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1. Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjögren's disease

Author: Lab Reumatologie/Klinische Immunologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, Boudjeniba, Cheïma, Soret, Perrine, Trutschel, Diana, Hamon, Antoine, Baloche, Valentin, Chassagnol, Bastien, Desvaux, Emiko, Bichat, Antoine, Aussy, Audrey, Moingeon, Philippe, Lefebvre, Céline, Hubert, Sandra, Alarcon-Riquelmé, Marta, Ng, Wan Fai, Gottenberg, Jacques Eric, Schwikowski, Benno, Bombardieri, Michele, van Roon, Joel A.G., Mariette, Xavier, Guedj, Mickaël, Birmele, Etienne, Laigle, Laurence, Becht, Etienne, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, Boudjeniba, Cheïma, Soret, Perrine, Trutschel, Diana, Hamon, Antoine, Baloche, Valentin, Chassagnol, Bastien, Desvaux, Emiko, Bichat, Antoine, Aussy, Audrey, Moingeon, Philippe, Lefebvre, Céline, Hubert, Sandra, Alarcon-Riquelmé, Marta, Ng, Wan Fai, Gottenberg, Jacques Eric, Schwikowski, Benno, Bombardieri, Michele, van Roon, Joel A.G., Mariette, Xavier, Guedj, Mickaël, Birmele, Etienne, Laigle, Laurence, and Becht, Etienne
Published: 2024

2. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials.

Author: Siempos, Ilias, Siempos, Ilias, Kalil, Andre, Belhadi, Drifa, Veiga, Viviane, Cavalcanti, Alexandre, Branch-Elliman, Westyn, Papoutsi, Eleni, Gkirgkiris, Konstantinos, Xixi, Nikoleta, Kotanidou, Anastasia, Hermine, Olivier, Porcher, Raphaël, Mariette, Xavier, Siempos, Ilias, Siempos, Ilias, Kalil, Andre, Belhadi, Drifa, Veiga, Viviane, Cavalcanti, Alexandre, Branch-Elliman, Westyn, Papoutsi, Eleni, Gkirgkiris, Konstantinos, Xixi, Nikoleta, Kotanidou, Anastasia, Hermine, Olivier, Porcher, Raphaël, and Mariette, Xavier
Abstract: BACKGROUND: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. METHODS: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). FINDINGS: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61-1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64-1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09-0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. INTERPRETATION: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. FUNDING: Hellenic Foundation for Research and Innovation.
Published: 2024

3. The Sjögren's Working Group:The 2023 OMERACT meeting and provisional domain generation

Author: Gordon, Rachael A., Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A., Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan Fai, Mendonça, Jose Alexandre, Wallace, Daniel J., Shea, Beverley, Bruyn, George AW, Goodman, Susan M., Fisher, Benjamin A., Baldini, Chiara, Torralba, Karina D., Bootsma, Hendrika, Akpek, Esen K., Karakus, Sezen, Baer, Alan N., Chakravarty, Soumya D., Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, DiRenzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M., Hammitt, Katherine M., Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Luis, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H., Benyoussef, Anas, Masli, Sharmila, Lee, Adrian Y.S., Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, McCoy, Sara S., Seror, Raphaele, Gordon, Rachael A., Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A., Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan Fai, Mendonça, Jose Alexandre, Wallace, Daniel J., Shea, Beverley, Bruyn, George AW, Goodman, Susan M., Fisher, Benjamin A., Baldini, Chiara, Torralba, Karina D., Bootsma, Hendrika, Akpek, Esen K., Karakus, Sezen, Baer, Alan N., Chakravarty, Soumya D., Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, DiRenzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M., Hammitt, Katherine M., Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Luis, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H., Benyoussef, Anas, Masli, Sharmila, Lee, Adrian Y.S., Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, McCoy, Sara S., and Seror, Raphaele
Abstract: Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity, Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.
Published: 2024

4. Oral glucocorticoid use in patients with rheumatoid arthritis initiating TNF-inhibitors, tocilizumab or abatacept:Results from the international TOCERRA and PANABA observational collaborative studies

Author: Lauper, Kim, Mongin, Denis, Bergstra, Sytske Anne, Choquette, Denis, Codreanu, Catalin, Gottenberg, Jacques Eric, Kubo, Satoshi, Hetland, Merete Lund, Iannone, Florenzo, Kristianslund, Eirik K., Kvien, Tore K., Lukina, Galina, Mariette, Xavier, Nordström, Dan C., Pavelka, Karel, Pombo-Suarez, Manuel, Rotar, Ziga, Santos, Maria J., Tanaka, Yoshiya, Turesson, Carl, Courvoisier, Delphine S., Finckh, Axel, Gabay, Cem, Lauper, Kim, Mongin, Denis, Bergstra, Sytske Anne, Choquette, Denis, Codreanu, Catalin, Gottenberg, Jacques Eric, Kubo, Satoshi, Hetland, Merete Lund, Iannone, Florenzo, Kristianslund, Eirik K., Kvien, Tore K., Lukina, Galina, Mariette, Xavier, Nordström, Dan C., Pavelka, Karel, Pombo-Suarez, Manuel, Rotar, Ziga, Santos, Maria J., Tanaka, Yoshiya, Turesson, Carl, Courvoisier, Delphine S., Finckh, Axel, and Gabay, Cem
Abstract: Objective To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). Methods We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. Results A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48–0.87] for abatacept, and 1.04 [0.76–1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83–1.47] for abatacept, and 1.30 [0.96–1.78] for tocilizumab. Conclusion After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved., Objective: To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). Methods: We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. Results: A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48–0.87] for abatacept, and 1.04 [0.76–1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83–1.47] for abatacept, and 1.30 [0.96–1.78] for tocilizumab. Conclusion: After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved.
Published: 2024

5. Oral glucocorticoid use in patients with rheumatoid arthritis initiating TNF-inhibitors, tocilizumab or abatacept:Results from the international TOCERRA and PANABA observational collaborative studies

Author: Lauper, Kim, Mongin, Denis, Bergstra, Sytske Anne, Choquette, Denis, Codreanu, Catalin, Gottenberg, Jacques Eric, Kubo, Satoshi, Hetland, Merete Lund, Iannone, Florenzo, Kristianslund, Eirik K., Kvien, Tore K., Lukina, Galina, Mariette, Xavier, Nordström, Dan C., Pavelka, Karel, Pombo-Suarez, Manuel, Rotar, Ziga, Santos, Maria J., Tanaka, Yoshiya, Turesson, Carl, Courvoisier, Delphine S., Finckh, Axel, Gabay, Cem, Lauper, Kim, Mongin, Denis, Bergstra, Sytske Anne, Choquette, Denis, Codreanu, Catalin, Gottenberg, Jacques Eric, Kubo, Satoshi, Hetland, Merete Lund, Iannone, Florenzo, Kristianslund, Eirik K., Kvien, Tore K., Lukina, Galina, Mariette, Xavier, Nordström, Dan C., Pavelka, Karel, Pombo-Suarez, Manuel, Rotar, Ziga, Santos, Maria J., Tanaka, Yoshiya, Turesson, Carl, Courvoisier, Delphine S., Finckh, Axel, and Gabay, Cem
Abstract: Objective To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). Methods We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. Results A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48–0.87] for abatacept, and 1.04 [0.76–1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83–1.47] for abatacept, and 1.30 [0.96–1.78] for tocilizumab. Conclusion After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved., Objective: To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). Methods: We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. Results: A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48–0.87] for abatacept, and 1.04 [0.76–1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83–1.47] for abatacept, and 1.30 [0.96–1.78] for tocilizumab. Conclusion: After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved.
Published: 2024

6. The Sjögren's Working Group: The 2023 OMERACT meeting and provisional domain generation

Author: Gordon, Rachael A, Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A, Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan-Fai, Mendonça, Jose Alexandre, Wallace, Daniel J, Shea, Beverley, Bruyn, George Aw, Goodman, Susan M, Fisher, Benjamin A, Baldini, Chiara, Torralba, Karina D, Bootsma, Hendrika, Akpek, Esen K, Karakus, Sezen, Baer, Alan N, Chakravarty, Soumya D, Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, Direnzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M, Hammitt, Katherine M, Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Lui, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H, Benyoussef, Ana, Masli, Sharmila, Lee, Adrian Y S, Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, Mccoy, Sara S, Seror, Raphaele, D'Agostino, Maria-Antonietta (ORCID:0000-0002-5347-0060), Gordon, Rachael A, Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A, Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan-Fai, Mendonça, Jose Alexandre, Wallace, Daniel J, Shea, Beverley, Bruyn, George Aw, Goodman, Susan M, Fisher, Benjamin A, Baldini, Chiara, Torralba, Karina D, Bootsma, Hendrika, Akpek, Esen K, Karakus, Sezen, Baer, Alan N, Chakravarty, Soumya D, Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, Direnzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M, Hammitt, Katherine M, Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Lui, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H, Benyoussef, Ana, Masli, Sharmila, Lee, Adrian Y S, Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, Mccoy, Sara S, Seror, Raphaele, and D'Agostino, Maria-Antonietta (ORCID:0000-0002-5347-0060)
Abstract: Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.
Published: 2024

7. Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update

Author: MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Aletaha, Daniel, Kerschbaumer, Andreas, Kastrati, Kastriot, Dejaco, Christian, Dougados, Maxime, McInnes, Iain B., Sattar, Naveed, Stamm, Tanja A., Takeuchi, Tsutomu, Trauner, Michael, Van Der Heijde, Désirée, Voshaar, Marieke, Winthrop, Kevin L., Ravelli, Angelo, Betteridge, Neil, Burmester, Gerd Rüdiger R., Bijlsma, Johannes W.J., Bykerk, Vivian, Caporali, Roberto, Choy, Ernest H., Codreanu, Catalin, Combe, Bernard, Crow, Mary K., De Wit, Maarten, Emery, Paul, Fleischmann, Roy M., Gabay, Cem, Hetland, Merete Lund, Hyrich, Kimme L., Iagnocco, Annamaria, Isaacs, John D., Kremer, Joel M., Mariette, Xavier, Merkel, Peter A., Mysler, Eduardo F., Nash, Peter, Nurmohamed, Michael T., Pavelka, Karel, Poor, Gyula, Rubbert-Roth, Andrea, Schulze-Koops, Hendrik, Strangfeld, Anja, Tanaka, Yoshiya, Smolen, Josef S., MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Aletaha, Daniel, Kerschbaumer, Andreas, Kastrati, Kastriot, Dejaco, Christian, Dougados, Maxime, McInnes, Iain B., Sattar, Naveed, Stamm, Tanja A., Takeuchi, Tsutomu, Trauner, Michael, Van Der Heijde, Désirée, Voshaar, Marieke, Winthrop, Kevin L., Ravelli, Angelo, Betteridge, Neil, Burmester, Gerd Rüdiger R., Bijlsma, Johannes W.J., Bykerk, Vivian, Caporali, Roberto, Choy, Ernest H., Codreanu, Catalin, Combe, Bernard, Crow, Mary K., De Wit, Maarten, Emery, Paul, Fleischmann, Roy M., Gabay, Cem, Hetland, Merete Lund, Hyrich, Kimme L., Iagnocco, Annamaria, Isaacs, John D., Kremer, Joel M., Mariette, Xavier, Merkel, Peter A., Mysler, Eduardo F., Nash, Peter, Nurmohamed, Michael T., Pavelka, Karel, Poor, Gyula, Rubbert-Roth, Andrea, Schulze-Koops, Hendrik, Strangfeld, Anja, Tanaka, Yoshiya, and Smolen, Josef S.
Published: 2023

8. Machine learning identifies a profile of inadequate responder to methotrexate in rheumatoid arthritis

Author: Duquesne, Julien, Bouget, Vincent, Cournède, Paul Henry, Fautrel, Bruno, Guillemin, Francis, De Jong, Pascal H.P., Heutz, Judith W., Verstappen, Marloes, Van Der Helm-Van Mil, Annette H.M., Mariette, Xavier, Bitoun, Samuel, Duquesne, Julien, Bouget, Vincent, Cournède, Paul Henry, Fautrel, Bruno, Guillemin, Francis, De Jong, Pascal H.P., Heutz, Judith W., Verstappen, Marloes, Van Der Helm-Van Mil, Annette H.M., Mariette, Xavier, and Bitoun, Samuel
Abstract: Objectives: Around 30% of patients with RA have an inadequate response to MTX. We aimed to use routine clinical and biological data to build machine learning models predicting EULAR inadequate response to MTX and to identify simple predictive biomarkers. Methods: Models were trained on RA patients fulfilling the 2010 ACR/EULAR criteria from the ESPOIR and Leiden EAC cohorts to predict the EULAR response at 9 months (± 6 months). Several models were compared on the training set using the AUROC. The best model was evaluated on an external validation cohort (tREACH). The model's predictions were explained using Shapley values to extract a biomarker of inadequate response. Results: We included 493 therapeutic sequences from ESPOIR, 239 from EAC and 138 from tREACH. The model selected DAS28, Lymphocytes, Creatininemia, Leucocytes, AST, ALT, swollen joint count and corticosteroid co-treatment as predictors. The model reached an AUROC of 0.72 [95% CI (0.63, 0.80)] on the external validation set, where 70% of patients were responders to MTX. Patients predicted as inadequate responders had only 38% [95% CI (20%, 58%)] chance to respond and using the algorithm to decide to initiate MTX would decrease inadequate-response rate from 30% to 23% [95% CI: (17%, 29%)]. A biomarker was identified in patients with moderate or high activity (DAS28 > 3.2): patients with a lymphocyte count superior to 2000 cells/mm3 are significantly less likely to respond. Conclusion: Our study highlights the usefulness of machine learning in unveiling subgroups of inadequate responders to MTX to guide new therapeutic strategies. Further work is needed to validate this approach.
Published: 2023

9. Hyperosmolar Environment and Salivary Gland Epithelial Cells Increase Extra-cellular Matrix Remodeling and Lymphocytic Infiltration in Sjögren’s Syndrome

Author: European Advanced Course and Conference on Immunology (Rouen), Rivière, Elodie, Chivasso, Clara, Pascaud, Juliette, Bechara, Rami, Ly, Bineta, Delporte, Christine, Mariette, Xavier, Nocturne, Gaetane, European Advanced Course and Conference on Immunology (Rouen), Rivière, Elodie, Chivasso, Clara, Pascaud, Juliette, Bechara, Rami, Ly, Bineta, Delporte, Christine, Mariette, Xavier, and Nocturne, Gaetane
Abstract: info:eu-repo/semantics/nonPublished
Published: 2023

10. Fabrication and desired properties of conductive hydrogel dressings for wound healing

Author: Nie, Lei, Wei, Qianqian, Li, Jingyu, Deng, Yaling, He, Xiaorui, Gao, Xinyue, Mariette, Xavier, Liu, Shuang, Sun, Yanfang, Jiang, Guohua, Okoro, Oseweuba Valentine, Shavandi, Amin, Jing, Shengli, Nie, Lei, Wei, Qianqian, Li, Jingyu, Deng, Yaling, He, Xiaorui, Gao, Xinyue, Mariette, Xavier, Liu, Shuang, Sun, Yanfang, Jiang, Guohua, Okoro, Oseweuba Valentine, Shavandi, Amin, and Jing, Shengli
Abstract: Conductive hydrogels are recognized as promising materials for wound healing. Valuable properties of conductive hydrogels suggest the possibility of their use as an alternative wound dressing to traditional dressings such as bandages., info:eu-repo/semantics/published
Published: 2023

11. Hyperosmolar environment and salivary gland epithelial cells increase extra-cellular matrix remodeling and lymphocytic infiltration in Sjögren’s syndrome.

Author: Rivière, Elodie, Chivasso, Clara, Pascaud, Juliette, Bechara, Rami, Ly, Bineta, Delporte, Christine, Mariette, Xavier, Nocturne, Gaetane, Rivière, Elodie, Chivasso, Clara, Pascaud, Juliette, Bechara, Rami, Ly, Bineta, Delporte, Christine, Mariette, Xavier, and Nocturne, Gaetane
Abstract: Salivary gland epithelial cells (SGECs) play an active role in primary Sjogren's syndrome (pSS) pathogenesis. Quantitative and qualitative abnormalities of saliva might expose SGECs to chronic hyperosmolarity. We aimed to decipher the links between hyperosmolar stimulation of SGECs and lymphocytic infiltration of the salivary glands (SG) observed in pSS. RNAseq was performed on NS-SV-AC cells stimulated with hyperosmolar media containing NaCl (100 mM) or sucrose (200 mM), or with iso-osmolar (Iso) medium. RNAseq was performed on primary cultured SGECs from pSS and controls, in the presence or not of B cells. Hyperosmolar stimulation of NS-SV-AC-cells identified an upregulation of interferon-induced (MX1, IFIT2) and MMPs genes. Enrichment analysis revealed an over-representation of fibrosis pathway. In parallel, RNAseq of SGECs comparing pSS to controls identified an over-representation of a pathway involving MMPs. Given the unexpected upregulation of collagen (COL3A1, COL1A2) and ADAMTS genes in pSS SGECs, we hypothesized that SGECs might undergo epithelial-mesenchymal transition. ZEB2 was upregulated and SLUG was down regulated in SGECs from pSS versus controls. MMP24 and ZEB2 were higher in SGECs from pSS with a focus score ≥1 versus <1. Lastly, SGECs cocultured with B cells expressed higher levels of COL1A2. These results suggest the existence of a vicious circle. Alteration of SGECs in pSS participates in the establishment of a hyperosmolar microenvironment, which in turn promotes SGECs transcriptomic modifications. These modifications include extracellular matrix remodeling and promote SG lymphocytic infiltration., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2023

12. Development and preliminary validation of the Sjögren's Tool for Assessing Response (STAR): a consensual composite score for assessing treatment effect in primary Sjögren's syndrome

Author: Translational Immunology, MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Lab Reumatologie/Klinische Immunologie, Seror, Raphaele, Baron, Gabriel, Camus, Marine, Cornec, Divi, Perrodeau, Elodie, Bowman, Simon J., Bombardieri, Michele, Bootsma, Hendrika, Gottenberg, Jacques Eric, Fisher, Benjamin, Hueber, Wolfgang, Van Roon, Joel A., Devauchelle-Pensec, Valérie, Gergely, Peter, Mariette, Xavier, Porcher, Raphael, Translational Immunology, MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Lab Reumatologie/Klinische Immunologie, Seror, Raphaele, Baron, Gabriel, Camus, Marine, Cornec, Divi, Perrodeau, Elodie, Bowman, Simon J., Bombardieri, Michele, Bootsma, Hendrika, Gottenberg, Jacques Eric, Fisher, Benjamin, Hueber, Wolfgang, Van Roon, Joel A., Devauchelle-Pensec, Valérie, Gergely, Peter, Mariette, Xavier, and Porcher, Raphael
Published: 2022

13. Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance.

Author: Ugarte-Gil, Manuel Francisco, Ugarte-Gil, Manuel Francisco, Alarcón, Graciela S, Izadi, Zara, Duarte-García, Ali, Reátegui-Sokolova, Cristina, Clarke, Ann Elaine, Wise, Leanna, Pons-Estel, Guillermo J, Santos, Maria Jose, Bernatsky, Sasha, Ribeiro, Sandra Lúcia Euzébio, Al Emadi, Samar, Sparks, Jeffrey A, Hsu, Tiffany Y-T, Patel, Naomi J, Gilbert, Emily L, Valenzuela-Almada, Maria O, Jönsen, Andreas, Landolfi, Gianpiero, Fredi, Micaela, Goulenok, Tiphaine, Devaux, Mathilde, Mariette, Xavier, Queyrel, Viviane, Romão, Vasco C, Sequeira, Graca, Hasseli, Rebecca, Hoyer, Bimba, Voll, Reinhard E, Specker, Christof, Baez, Roberto, Castro-Coello, Vanessa, Maldonado Ficco, Hernan, Reis Neto, Edgard Torres, Ferreira, Gilda Aparecida Aparecida, Monticielo, Odirlei Andre André, Sirotich, Emily, Liew, Jean, Hausmann, Jonathan, Sufka, Paul, Grainger, Rebecca, Bhana, Suleman, Costello, Wendy, Wallace, Zachary S, Jacobsohn, Lindsay, Taylor, Tiffany, Ja, Clairissa, Strangfeld, Anja, Mateus, Elsa F, Hyrich, Kimme L, Carmona, Loreto, Lawson-Tovey, Saskia, Kearsley-Fleet, Lianne, Schäfer, Martin, Machado, Pedro M, Robinson, Philip C, Gianfrancesco, Milena, Yazdany, Jinoos, Ugarte-Gil, Manuel Francisco, Ugarte-Gil, Manuel Francisco, Alarcón, Graciela S, Izadi, Zara, Duarte-García, Ali, Reátegui-Sokolova, Cristina, Clarke, Ann Elaine, Wise, Leanna, Pons-Estel, Guillermo J, Santos, Maria Jose, Bernatsky, Sasha, Ribeiro, Sandra Lúcia Euzébio, Al Emadi, Samar, Sparks, Jeffrey A, Hsu, Tiffany Y-T, Patel, Naomi J, Gilbert, Emily L, Valenzuela-Almada, Maria O, Jönsen, Andreas, Landolfi, Gianpiero, Fredi, Micaela, Goulenok, Tiphaine, Devaux, Mathilde, Mariette, Xavier, Queyrel, Viviane, Romão, Vasco C, Sequeira, Graca, Hasseli, Rebecca, Hoyer, Bimba, Voll, Reinhard E, Specker, Christof, Baez, Roberto, Castro-Coello, Vanessa, Maldonado Ficco, Hernan, Reis Neto, Edgard Torres, Ferreira, Gilda Aparecida Aparecida, Monticielo, Odirlei Andre André, Sirotich, Emily, Liew, Jean, Hausmann, Jonathan, Sufka, Paul, Grainger, Rebecca, Bhana, Suleman, Costello, Wendy, Wallace, Zachary S, Jacobsohn, Lindsay, Taylor, Tiffany, Ja, Clairissa, Strangfeld, Anja, Mateus, Elsa F, Hyrich, Kimme L, Carmona, Loreto, Lawson-Tovey, Saskia, Kearsley-Fleet, Lianne, Schäfer, Martin, Machado, Pedro M, Robinson, Philip C, Gianfrancesco, Milena, and Yazdany, Jinoos
Abstract: AimTo determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19.MethodsPeople with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity.ResultsA total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab.ConclusionsMore severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.
Published: 2022

14. Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function., Funding Agencies|National Institutes of Health (NIH) [HHSN268200782096C, HHSN268201100011I, HHSN268201200008I, R01AR073855, R01AR065953, R01AR074310, P50AR060804, R01AR050782, R01DE018209, R33AR076803, R21AR079089]; NIDCR Sjogrens Syndrome Clinic; NIDCR Division of Intramural Research at the National Institutes of Health funds [Z01-DE000704]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanys Excellence Strategy [EXC 2155, 390874280]; Research Council of Norway (Oslo, Norway) [240421, 316120]; Western Norway Regional Health Authority (Helse Vest) [911807, 912043]; Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; King Gustav Vs 80-year Foundation; Swedish Society of Medicine; Swedish Cancer Society; Sjogrens Syndrome Foundation; Phileona Foundation; Stockholm County Council; Swedish Research Council [2017-000641]; Assistance Publique-Hopitaux de Paris (Ministry of Health) [P060228]; French society of Rheumatology; National Institute of Aging [RC2 AG036495, RC4 AG039029]; National Institute of Dental and Craniofacial Research (NIDCR); National Eye Institute; Office of Research on Womens Health [N01-DE-32636]; NIDCR through CIDRs NIH contract; FOREUM Foundation for Research in Rheumatology
Published: 2022
Full Text: View/download PDF

15. Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin, V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin, V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
Published: 2022
Full Text: View/download PDF

16. Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin, V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin, V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
Published: 2022
Full Text: View/download PDF

17. Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function., Funding Agencies|National Institutes of Health (NIH) [HHSN268200782096C, HHSN268201100011I, HHSN268201200008I, R01AR073855, R01AR065953, R01AR074310, P50AR060804, R01AR050782, R01DE018209, R33AR076803, R21AR079089]; NIDCR Sjogrens Syndrome Clinic; NIDCR Division of Intramural Research at the National Institutes of Health funds [Z01-DE000704]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanys Excellence Strategy [EXC 2155, 390874280]; Research Council of Norway (Oslo, Norway) [240421, 316120]; Western Norway Regional Health Authority (Helse Vest) [911807, 912043]; Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; King Gustav Vs 80-year Foundation; Swedish Society of Medicine; Swedish Cancer Society; Sjogrens Syndrome Foundation; Phileona Foundation; Stockholm County Council; Swedish Research Council [2017-000641]; Assistance Publique-Hopitaux de Paris (Ministry of Health) [P060228]; French society of Rheumatology; National Institute of Aging [RC2 AG036495, RC4 AG039029]; National Institute of Dental and Craniofacial Research (NIDCR); National Eye Institute; Office of Research on Womens Health [N01-DE-32636]; NIDCR through CIDRs NIH contract; FOREUM Foundation for Research in Rheumatology
Published: 2022
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18. Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin, V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin, V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
Published: 2022
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19. Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry.

Author: UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Machado, Pedro M, Lawson-Tovey, Saskia, Strangfeld, Anja, Mateus, Elsa F, Hyrich, Kimme L, Gossec, Laure, Carmona, Loreto, Rodrigues, Ana, Raffeiner, Bernd, Duarte, Catia, Hachulla, Eric, Veillard, Eric, Strakova, Eva, Burmester, Gerd R, Yardımcı, Gözde Kübra, Gomez-Puerta, Jose A, Zepa, Julija, Kearsley-Fleet, Lianne, Trefond, Ludovic, Cunha, Maria, Mosca, Marta, Cornalba, Martina, Soubrier, Martin, Roux, Nicolas, Brocq, Olivier, Durez, Patrick, Conway, Richard, Goulenok, Tiphaine, Bijlsma, Johannes Wj, McInnes, Iain B, Mariette, Xavier, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Machado, Pedro M, Lawson-Tovey, Saskia, Strangfeld, Anja, Mateus, Elsa F, Hyrich, Kimme L, Gossec, Laure, Carmona, Loreto, Rodrigues, Ana, Raffeiner, Bernd, Duarte, Catia, Hachulla, Eric, Veillard, Eric, Strakova, Eva, Burmester, Gerd R, Yardımcı, Gözde Kübra, Gomez-Puerta, Jose A, Zepa, Julija, Kearsley-Fleet, Lianne, Trefond, Ludovic, Cunha, Maria, Mosca, Marta, Cornalba, Martina, Soubrier, Martin, Roux, Nicolas, Brocq, Olivier, Durez, Patrick, Conway, Richard, Goulenok, Tiphaine, Bijlsma, Johannes Wj, McInnes, Iain B, and Mariette, Xavier
Abstract: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD). Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively. The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD). The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.
Published: 2022

20. CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi, Hellberg, Sandra, Bhai Mehta, Ratnesh, Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm, Benson, Mikael, Berg, Göran, Jenmalm, Maria, Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi, Hellberg, Sandra, Bhai Mehta, Ratnesh, Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm, Benson, Mikael, Berg, Göran, Jenmalm, Maria, Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases., Funding Agencies|Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [SB16-0011]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [K2013-61X-22310-01-4, 2015-030807, 2018-02776]; Lions research grant [Liu-2012-01948]
Published: 2022
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21. CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi, Hellberg, Sandra, Bhai Mehta, Ratnesh, Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm, Benson, Mikael, Berg, Göran, Jenmalm, Maria, Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi, Hellberg, Sandra, Bhai Mehta, Ratnesh, Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm, Benson, Mikael, Berg, Göran, Jenmalm, Maria, Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases., Funding Agencies|Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [SB16-0011]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [K2013-61X-22310-01-4, 2015-030807, 2018-02776]; Lions research grant [Liu-2012-01948]
Published: 2022
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22. The added value of a European Reference Network on rare and complex connective tissue and musculoskeletal diseases: insights after the first 5 years of the ERN ReCONNET.

Author: UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Talarico, Rosaria, Aguilera, Silvia, Alexander, Tobias, Amoura, Zahir, Andersen, Janette, Arnaud, Laurent, Avcin, Tadej, Marsal Barril, Sara, Beretta, Lorenzo, Bombardieri, Stefano, Bortoluzzi, Alessandra, Bouillot, Coralie, Bulina, Inita, Burmester, Gerd R, Cannizzo, Sara, Cavagna, Lorenzo, Chaigne, Benjamin, Cornet, Alain, Corti, Paolo, Costedoat-Chalumeau, Nathalie, Dāvidsone, Zane, Doria, Andrea, Fenech, Carol, Ferraris, Alessandro, Fischer-Betz, Rebecca, Fonseca, João Eurico, Frank, Charissa, Gaglioti, Andrea, Galetti, Ilaria, Guimarães, Vera, Hachulla, Eric, Holmner, Monica, Houssiau, Frederic, Iaccarino, Luca, Jacobsen, Søren, Limper, Maarten, Malfait, Fransiska, Mariette, Xavier, Marinello, Diana, Martin, Thierry, Matthews, Lisa, Matucci-Cerinic, Marco, Meyer, Alain, Milas-Ahić, Jasminka, Moinzadeh, Pia, Montecucco, Carlomaurizio, Mouthon, Luc, Müller-Ladner, Ulf, Nagy, György, Patarata, Eunice, Pileckyte, Margarita, Pruunsild, Chris, Rednic, Simona, Romão, Vasco C, Schneider, Matthias, Scirè, Carlo Alberto, Smith, Vanessa, Sulli, Alberto, Tamirou, Farah, Tani, Chiara, Taruscio, Domenica, Taulaigo, Anna V, Tincani, Angela, Ticciati, Simone, Turchetti, Giuseppe, van Hagen, P Martin, van Laar, Jacob M, Viera, Ana, de Vries-Bouwstra, Jeska K, Zschocke, Johannes, Cutolo, Maurizio, Mosca, Marta, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Talarico, Rosaria, Aguilera, Silvia, Alexander, Tobias, Amoura, Zahir, Andersen, Janette, Arnaud, Laurent, Avcin, Tadej, Marsal Barril, Sara, Beretta, Lorenzo, Bombardieri, Stefano, Bortoluzzi, Alessandra, Bouillot, Coralie, Bulina, Inita, Burmester, Gerd R, Cannizzo, Sara, Cavagna, Lorenzo, Chaigne, Benjamin, Cornet, Alain, Corti, Paolo, Costedoat-Chalumeau, Nathalie, Dāvidsone, Zane, Doria, Andrea, Fenech, Carol, Ferraris, Alessandro, Fischer-Betz, Rebecca, Fonseca, João Eurico, Frank, Charissa, Gaglioti, Andrea, Galetti, Ilaria, Guimarães, Vera, Hachulla, Eric, Holmner, Monica, Houssiau, Frederic, Iaccarino, Luca, Jacobsen, Søren, Limper, Maarten, Malfait, Fransiska, Mariette, Xavier, Marinello, Diana, Martin, Thierry, Matthews, Lisa, Matucci-Cerinic, Marco, Meyer, Alain, Milas-Ahić, Jasminka, Moinzadeh, Pia, Montecucco, Carlomaurizio, Mouthon, Luc, Müller-Ladner, Ulf, Nagy, György, Patarata, Eunice, Pileckyte, Margarita, Pruunsild, Chris, Rednic, Simona, Romão, Vasco C, Schneider, Matthias, Scirè, Carlo Alberto, Smith, Vanessa, Sulli, Alberto, Tamirou, Farah, Tani, Chiara, Taruscio, Domenica, Taulaigo, Anna V, Tincani, Angela, Ticciati, Simone, Turchetti, Giuseppe, van Hagen, P Martin, van Laar, Jacob M, Viera, Ana, de Vries-Bouwstra, Jeska K, Zschocke, Johannes, Cutolo, Maurizio, and Mosca, Marta
Abstract: In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients.It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.
Published: 2022

23. SARS-CoV-2 vaccine safety in adolescents with inflammatory rheumatic and musculoskeletal diseases and adults with juvenile idiopathic arthritis: data from the EULAR COVAX physician-reported registry

Author: UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Lawson-Tovey, Saskia, Machado, Pedro M, Strangfeld, Anja, Mateus, Elsa, Gossec, Laure, Carmona, Loreto, Raffeiner, Bernd, Bulina, Inita, Clemente, Daniel, Zepa, Julija, Rodrigues, Ana M., Mariette, Xavier, Hyrich, Kimme L, Durez, Patrick, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Lawson-Tovey, Saskia, Machado, Pedro M, Strangfeld, Anja, Mateus, Elsa, Gossec, Laure, Carmona, Loreto, Raffeiner, Bernd, Bulina, Inita, Clemente, Daniel, Zepa, Julija, Rodrigues, Ana M., Mariette, Xavier, Hyrich, Kimme L, and Durez, Patrick
Abstract: Background There is a lack of data on SARS-CoV-2 vaccination safety in children and young people (CYP) with rheumatic and musculoskeletal diseases (RMDs). Current vaccination guidance is based on data from adults with RMDs or CYP without RMDs. Objectives To describe the safety of SARS-COV-2 vaccination in adolescents with inflammatory RMDs and adults with juvenile idiopathic arthritis (JIA). Methods We described patient characteristics, flares and adverse events (AEs) in adolescent cases under 18 with inflammatory RMDs and adult cases aged 18 or above with JIA submitted to the European Alliance of Associations for Rheumatology COVAX registry. Results A total of 110 cases were reported to the registry. Thirty-six adolescent cases were reported from four countries, most with JIA (42%). Over half (56%) reported early reactogenic-like AEs. One mild polyarthralgia flare and one serious AE of special interest (malaise) were reported. No CYP reported SARS-CoV-2 infection postvaccination. Seventy-four adult JIA cases were reported from 11 countries. Almost two-thirds (62%) reported early reactogenic-like AEs and two flares were reported (mild polyarthralgia and moderate uveitis). No serious AEs of special interest were reported among adults with JIA. Three female patients aged 20–30 years were diagnosed with SARS-CoV-2 postvaccination; all fully recovered. Conclusions This is an important contribution to research on SARS-CoV-2 vaccine safety in adolescents with RMDs and adults with JIA. It is important to note the low frequency of disease flares, serious AEs and SARS-CoV-2 reinfection seen in both populations, although the dataset is limited by its size.
Published: 2022

24. Author Correction: Genome-wide association study identifies Sjogrens risk loci with functional implications in immune and glandular cells (vol 13, 4287, 2022)

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Published: 2022
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25. Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance.

Author: Ugarte-Gil, Manuel Francisco, Ugarte-Gil, Manuel Francisco, Alarcón, Graciela S, Izadi, Zara, Duarte-García, Ali, Reátegui-Sokolova, Cristina, Clarke, Ann Elaine, Wise, Leanna, Pons-Estel, Guillermo J, Santos, Maria Jose, Bernatsky, Sasha, Ribeiro, Sandra Lúcia Euzébio, Al Emadi, Samar, Sparks, Jeffrey A, Hsu, Tiffany Y-T, Patel, Naomi J, Gilbert, Emily L, Valenzuela-Almada, Maria O, Jönsen, Andreas, Landolfi, Gianpiero, Fredi, Micaela, Goulenok, Tiphaine, Devaux, Mathilde, Mariette, Xavier, Queyrel, Viviane, Romão, Vasco C, Sequeira, Graca, Hasseli, Rebecca, Hoyer, Bimba, Voll, Reinhard E, Specker, Christof, Baez, Roberto, Castro-Coello, Vanessa, Maldonado Ficco, Hernan, Reis Neto, Edgard Torres, Ferreira, Gilda Aparecida Aparecida, Monticielo, Odirlei Andre André, Sirotich, Emily, Liew, Jean, Hausmann, Jonathan, Sufka, Paul, Grainger, Rebecca, Bhana, Suleman, Costello, Wendy, Wallace, Zachary S, Jacobsohn, Lindsay, Taylor, Tiffany, Ja, Clairissa, Strangfeld, Anja, Mateus, Elsa F, Hyrich, Kimme L, Carmona, Loreto, Lawson-Tovey, Saskia, Kearsley-Fleet, Lianne, Schäfer, Martin, Machado, Pedro M, Robinson, Philip C, Gianfrancesco, Milena, Yazdany, Jinoos, Ugarte-Gil, Manuel Francisco, Ugarte-Gil, Manuel Francisco, Alarcón, Graciela S, Izadi, Zara, Duarte-García, Ali, Reátegui-Sokolova, Cristina, Clarke, Ann Elaine, Wise, Leanna, Pons-Estel, Guillermo J, Santos, Maria Jose, Bernatsky, Sasha, Ribeiro, Sandra Lúcia Euzébio, Al Emadi, Samar, Sparks, Jeffrey A, Hsu, Tiffany Y-T, Patel, Naomi J, Gilbert, Emily L, Valenzuela-Almada, Maria O, Jönsen, Andreas, Landolfi, Gianpiero, Fredi, Micaela, Goulenok, Tiphaine, Devaux, Mathilde, Mariette, Xavier, Queyrel, Viviane, Romão, Vasco C, Sequeira, Graca, Hasseli, Rebecca, Hoyer, Bimba, Voll, Reinhard E, Specker, Christof, Baez, Roberto, Castro-Coello, Vanessa, Maldonado Ficco, Hernan, Reis Neto, Edgard Torres, Ferreira, Gilda Aparecida Aparecida, Monticielo, Odirlei Andre André, Sirotich, Emily, Liew, Jean, Hausmann, Jonathan, Sufka, Paul, Grainger, Rebecca, Bhana, Suleman, Costello, Wendy, Wallace, Zachary S, Jacobsohn, Lindsay, Taylor, Tiffany, Ja, Clairissa, Strangfeld, Anja, Mateus, Elsa F, Hyrich, Kimme L, Carmona, Loreto, Lawson-Tovey, Saskia, Kearsley-Fleet, Lianne, Schäfer, Martin, Machado, Pedro M, Robinson, Philip C, Gianfrancesco, Milena, and Yazdany, Jinoos
Abstract: AimTo determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19.MethodsPeople with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity.ResultsA total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab.ConclusionsMore severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.
Published: 2022

26. CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi, Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi, Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases., CC BY 4.0Contact Sandra Hellberg Email iconsandra.hellberg@liu.sePublished online: 04 Oct 2021Copyright © 2022 Informa UK Limited This work was supported by the Swedish Foundation for Strategic Research (SB16-0011), Swedish Research Council (K2013-61X-22310-01-4, 2015-030807, 2018-02776) and Lions research grant (Liu-2012-01948).
Published: 2022
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27. CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi, Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi, Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases., CC BY 4.0Contact Sandra Hellberg Email iconsandra.hellberg@liu.sePublished online: 04 Oct 2021Copyright © 2022 Informa UK Limited This work was supported by the Swedish Foundation for Strategic Research (SB16-0011), Swedish Research Council (K2013-61X-22310-01-4, 2015-030807, 2018-02776) and Lions research grant (Liu-2012-01948).
Published: 2022
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28. Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin, V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin, V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
Published: 2022
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29. Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Author: Hernandez-Molina, Gabriela, Kostov, Belchin, Brito-Zeron, Pilar, Vissink, Arjan, Mandl, Thomas, Hinrichs, Anneline C., Quartuccio, Luca, Baldini, Chiara, Seror, Raphaele, Szanto, Antonia, Isenberg, David, Gerli, Roberto, Nordmark, Gunnel, Rasmussen, Astrid, Solans-Laque, Roser, Hofauer, Benedikt, Sene, Damien, Pasoto, Sandra G., Rischmueller, Maureen, Praprotnik, Sonja, Gheita, Tamer A., Danda, Debashish, Armagan, Berkan, Suzuki, Yasunori, Valim, Valeria, Devauchelle-Pensec, Valerie, Retamozo, Soledad, Kvarnstrom, Marika, Sebastian, Agata, Atzeni, Fabiola, Giacomelli, Roberto, Carsons, Steven E., Kwok, Seung-Ki, Nakamura, Hideki, Moca Trevisani, Virginia Fernandes, Flores-Chavez, Alejandra, Mariette, Xavier, Ramos-Casals, Manuel, Hernandez-Molina, Gabriela, Kostov, Belchin, Brito-Zeron, Pilar, Vissink, Arjan, Mandl, Thomas, Hinrichs, Anneline C., Quartuccio, Luca, Baldini, Chiara, Seror, Raphaele, Szanto, Antonia, Isenberg, David, Gerli, Roberto, Nordmark, Gunnel, Rasmussen, Astrid, Solans-Laque, Roser, Hofauer, Benedikt, Sene, Damien, Pasoto, Sandra G., Rischmueller, Maureen, Praprotnik, Sonja, Gheita, Tamer A., Danda, Debashish, Armagan, Berkan, Suzuki, Yasunori, Valim, Valeria, Devauchelle-Pensec, Valerie, Retamozo, Soledad, Kvarnstrom, Marika, Sebastian, Agata, Atzeni, Fabiola, Giacomelli, Roberto, Carsons, Steven E., Kwok, Seung-Ki, Nakamura, Hideki, Moca Trevisani, Virginia Fernandes, Flores-Chavez, Alejandra, Mariette, Xavier, and Ramos-Casals, Manuel
Abstract: Objective To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.
Published: 2022
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30. Author Correction: Genome-wide association study identifies Sjogrens risk loci with functional implications in immune and glandular cells (vol 13, 4287, 2022)

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Published: 2022
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31. Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis

Author: Ishigaki, Kazuyoshi, Sakaue, Saori, Terao, Chikashi, Luo, Yang, Sonehara, Kyuto, Yamaguchi, Kensuke, Amariuta, Tiffany, Too, Chun Lai, Laufer, Vincent A., Scott, Ian C., Viatte, Sebastien, Takahashi, Meiko, Ohmura, Koichiro, Murasawa, Akira, Hashimoto, Motomu, Ito, Hiromu, Hammoudeh, Mohammed, Emadi, Samar Al, Masri, Basel K., Halabi, Hussein, Badsha, Humeira, Uthman, Imad W., Wu, Xin, Lin, Li, Li, Ting, Plant, Darren, Barton, Anne, Orozco, Gisela, Verstappen, Suzanne M. M., Bowes, John, MacGregor, Alexander J., Honda, Suguru, Koido, Masaru, Tomizuka, Kohei, Kamatani, Yoichiro, Tanaka, Hiroaki, Tanaka, Eiichi, Suzuki, Akari, Maeda, Yuichi, Yamamoto, Kenichi, Miyawaki, Satoru, Xie, Gang, Zhang, Jinyi, Amos, Christopher I., Keystone, Edward, Wolbink, Gertjan, van der Horst-Bruinsma, Irene, Cui, Jing, Liao, Katherine P., Carroll, Robert J., Lee, Hye-Soon, Bang, So-Young, Siminovitch, Katherine A., de Vries, Niek, Alfredsson, Lars, Rantapää-Dahlqvist, Solbritt, Karlson, Elizabeth W., Bae, Sang-Cheol, Kimberly, Robert P., Edberg, Jeffrey C., Mariette, Xavier, Huizinga, Tom, Dieudé, Philippe, Schneider, Matthias, Kerick, Martin, Denny, Joshua C., Matsuda, Koichi, Matsuo, Keitaro, Mimori, Tsuneyo, Matsuda, Fumihiko, Fujio, Keishi, Tanaka, Yoshiya, Kumanogoh, Atsushi, Traylor, Matthew, Lewis, Cathryn M., Eyre, Stephen, Xu, Huji, Saxena, Richa, Arayssi, Thurayya, Kochi, Yuta, Ikari, Katsunori, Harigai, Masayoshi, Gregersen, Peter K., Yamamoto, Kazuhiko, Louis Bridges, S., Padyukov, Leonid, Martin, Javier, Klareskog, Lars, Okada, Yukinori, Raychaudhuri, Soumya, Ishigaki, Kazuyoshi, Sakaue, Saori, Terao, Chikashi, Luo, Yang, Sonehara, Kyuto, Yamaguchi, Kensuke, Amariuta, Tiffany, Too, Chun Lai, Laufer, Vincent A., Scott, Ian C., Viatte, Sebastien, Takahashi, Meiko, Ohmura, Koichiro, Murasawa, Akira, Hashimoto, Motomu, Ito, Hiromu, Hammoudeh, Mohammed, Emadi, Samar Al, Masri, Basel K., Halabi, Hussein, Badsha, Humeira, Uthman, Imad W., Wu, Xin, Lin, Li, Li, Ting, Plant, Darren, Barton, Anne, Orozco, Gisela, Verstappen, Suzanne M. M., Bowes, John, MacGregor, Alexander J., Honda, Suguru, Koido, Masaru, Tomizuka, Kohei, Kamatani, Yoichiro, Tanaka, Hiroaki, Tanaka, Eiichi, Suzuki, Akari, Maeda, Yuichi, Yamamoto, Kenichi, Miyawaki, Satoru, Xie, Gang, Zhang, Jinyi, Amos, Christopher I., Keystone, Edward, Wolbink, Gertjan, van der Horst-Bruinsma, Irene, Cui, Jing, Liao, Katherine P., Carroll, Robert J., Lee, Hye-Soon, Bang, So-Young, Siminovitch, Katherine A., de Vries, Niek, Alfredsson, Lars, Rantapää-Dahlqvist, Solbritt, Karlson, Elizabeth W., Bae, Sang-Cheol, Kimberly, Robert P., Edberg, Jeffrey C., Mariette, Xavier, Huizinga, Tom, Dieudé, Philippe, Schneider, Matthias, Kerick, Martin, Denny, Joshua C., Matsuda, Koichi, Matsuo, Keitaro, Mimori, Tsuneyo, Matsuda, Fumihiko, Fujio, Keishi, Tanaka, Yoshiya, Kumanogoh, Atsushi, Traylor, Matthew, Lewis, Cathryn M., Eyre, Stephen, Xu, Huji, Saxena, Richa, Arayssi, Thurayya, Kochi, Yuta, Ikari, Katsunori, Harigai, Masayoshi, Gregersen, Peter K., Yamamoto, Kazuhiko, Louis Bridges, S., Padyukov, Leonid, Martin, Javier, Klareskog, Lars, Okada, Yukinori, and Raychaudhuri, Soumya
Abstract: Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10−8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.
Published: 2022
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32. Genome-wide association study identifies Sjögrens risk loci with functional implications in immune and glandular cells.

Author: Khatri, Bhuwan, Khatri, Bhuwan, Tessneer, Kandice, Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara, Baecklund, Eva, Brun, Johan, Bucher, Sara, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart, Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke, Johnsen, Svein, Jonsson, Malin, Kvarnström, Marika, Kelly, Jennifer, Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna, Taylor, Kimberly, Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel, Grundahl, Kiely, Hefner, Kimberly, Radfar, Lida, Lewis, David, Stone, Donald, Kaufman, C, Brennan, Michael, Guthridge, Joel, James, Judith, Scofield, R, Gaffney, Patrick, Criswell, Lindsey, Jonsson, Roland, Eriksson, Per, Bowman, Simon, Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A, Mariette, Xavier, Alarcon-Riquelme, Marta, Shiboski, Caroline, Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy, Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher, Khatri, Bhuwan, Khatri, Bhuwan, Tessneer, Kandice, Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara, Baecklund, Eva, Brun, Johan, Bucher, Sara, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart, Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke, Johnsen, Svein, Jonsson, Malin, Kvarnström, Marika, Kelly, Jennifer, Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna, Taylor, Kimberly, Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel, Grundahl, Kiely, Hefner, Kimberly, Radfar, Lida, Lewis, David, Stone, Donald, Kaufman, C, Brennan, Michael, Guthridge, Joel, James, Judith, Scofield, R, Gaffney, Patrick, Criswell, Lindsey, Jonsson, Roland, Eriksson, Per, Bowman, Simon, Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A, Mariette, Xavier, Alarcon-Riquelme, Marta, Shiboski, Caroline, Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy, Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher
Abstract: Sjögrens disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögrens cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.
Published: 2022

33. Author Correction: Genome-wide association study identifies Sjogrens risk loci with functional implications in immune and glandular cells (vol 13, 4287, 2022)

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Published: 2022
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34. Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function., Funding Agencies|National Institutes of Health (NIH) [HHSN268200782096C, HHSN268201100011I, HHSN268201200008I, R01AR073855, R01AR065953, R01AR074310, P50AR060804, R01AR050782, R01DE018209, R33AR076803, R21AR079089]; NIDCR Sjogrens Syndrome Clinic; NIDCR Division of Intramural Research at the National Institutes of Health funds [Z01-DE000704]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanys Excellence Strategy [EXC 2155, 390874280]; Research Council of Norway (Oslo, Norway) [240421, 316120]; Western Norway Regional Health Authority (Helse Vest) [911807, 912043]; Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; King Gustav Vs 80-year Foundation; Swedish Society of Medicine; Swedish Cancer Society; Sjogrens Syndrome Foundation; Phileona Foundation; Stockholm County Council; Swedish Research Council [2017-000641]; Assistance Publique-Hopitaux de Paris (Ministry of Health) [P060228]; French society of Rheumatology; National Institute of Aging [RC2 AG036495, RC4 AG039029]; National Institute of Dental and Craniofacial Research (NIDCR); National Eye Institute; Office of Research on Womens Health [N01-DE-32636]; NIDCR through CIDRs NIH contract; FOREUM Foundation for Research in Rheumatology
Published: 2022
Full Text: View/download PDF

35. CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi, Hellberg, Sandra, Bhai Mehta, Ratnesh, Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm, Benson, Mikael, Berg, Göran, Jenmalm, Maria, Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi, Hellberg, Sandra, Bhai Mehta, Ratnesh, Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm, Benson, Mikael, Berg, Göran, Jenmalm, Maria, Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases., Funding Agencies|Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [SB16-0011]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [K2013-61X-22310-01-4, 2015-030807, 2018-02776]; Lions research grant [Liu-2012-01948]
Published: 2022
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36. Author Correction: Genome-wide association study identifies Sjogrens risk loci with functional implications in immune and glandular cells (vol 13, 4287, 2022)

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Published: 2022
Full Text: View/download PDF

37. Author Correction: Genome-wide association study identifies Sjogrens risk loci with functional implications in immune and glandular cells (vol 13, 4287, 2022)

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Published: 2022
Full Text: View/download PDF

38. Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function., Funding Agencies|National Institutes of Health (NIH) [HHSN268200782096C, HHSN268201100011I, HHSN268201200008I, R01AR073855, R01AR065953, R01AR074310, P50AR060804, R01AR050782, R01DE018209, R33AR076803, R21AR079089]; NIDCR Sjogrens Syndrome Clinic; NIDCR Division of Intramural Research at the National Institutes of Health funds [Z01-DE000704]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanys Excellence Strategy [EXC 2155, 390874280]; Research Council of Norway (Oslo, Norway) [240421, 316120]; Western Norway Regional Health Authority (Helse Vest) [911807, 912043]; Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; King Gustav Vs 80-year Foundation; Swedish Society of Medicine; Swedish Cancer Society; Sjogrens Syndrome Foundation; Phileona Foundation; Stockholm County Council; Swedish Research Council [2017-000641]; Assistance Publique-Hopitaux de Paris (Ministry of Health) [P060228]; French society of Rheumatology; National Institute of Aging [RC2 AG036495, RC4 AG039029]; National Institute of Dental and Craniofacial Research (NIDCR); National Eye Institute; Office of Research on Womens Health [N01-DE-32636]; NIDCR through CIDRs NIH contract; FOREUM Foundation for Research in Rheumatology
Published: 2022
Full Text: View/download PDF

39. Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function., Funding Agencies|National Institutes of Health (NIH) [HHSN268200782096C, HHSN268201100011I, HHSN268201200008I, R01AR073855, R01AR065953, R01AR074310, P50AR060804, R01AR050782, R01DE018209, R33AR076803, R21AR079089]; NIDCR Sjogrens Syndrome Clinic; NIDCR Division of Intramural Research at the National Institutes of Health funds [Z01-DE000704]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanys Excellence Strategy [EXC 2155, 390874280]; Research Council of Norway (Oslo, Norway) [240421, 316120]; Western Norway Regional Health Authority (Helse Vest) [911807, 912043]; Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; King Gustav Vs 80-year Foundation; Swedish Society of Medicine; Swedish Cancer Society; Sjogrens Syndrome Foundation; Phileona Foundation; Stockholm County Council; Swedish Research Council [2017-000641]; Assistance Publique-Hopitaux de Paris (Ministry of Health) [P060228]; French society of Rheumatology; National Institute of Aging [RC2 AG036495, RC4 AG039029]; National Institute of Dental and Craniofacial Research (NIDCR); National Eye Institute; Office of Research on Womens Health [N01-DE-32636]; NIDCR through CIDRs NIH contract; FOREUM Foundation for Research in Rheumatology
Published: 2022
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40. Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells

Author: Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin, V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d'Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin, V, Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.
Abstract: Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
Published: 2022
Full Text: View/download PDF

41. A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren's syndrome

Author: Mariette, Xavier, Barone, Francesca, Baldini, Chiara, Bootsma, Hendrika, Clark, Kenneth L., De Vita, Salvatore, Gardner, David H., Henderson, Robert B., Herdman, Michael, Lerang, Karoline, Mistry, Prafull, Punwaney, Raj, Seror, Raphaele, Stone, John, van Daele, Paul L.A., van Maurik, André, Wisniacki, Nicolas, Roth, David A., Tak, Paul Peter, Mariette, Xavier, Barone, Francesca, Baldini, Chiara, Bootsma, Hendrika, Clark, Kenneth L., De Vita, Salvatore, Gardner, David H., Henderson, Robert B., Herdman, Michael, Lerang, Karoline, Mistry, Prafull, Punwaney, Raj, Seror, Raphaele, Stone, John, van Daele, Paul L.A., van Maurik, André, Wisniacki, Nicolas, Roth, David A., and Tak, Paul Peter
Abstract: BACKGROUND. Primary Sjögren's syndrome (pSS) is characterized by B cell hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment (e.g., belimumab) increases peripheral memory B cells; decreases naive, activated, and plasma B cell subsets; and increases stringency on B cell selection during reconstitution. Anti-CD20 therapeutics (e.g., rituximab) bind and deplete CD20-expressing B cells in circulation but are less effective in depleting tissue-resident CD20+ B cells. Combined, these 2 mechanisms may achieve synergistic effects. METHODS. This 68-week, phase II, double-blind study (GSK study 201842) randomized 86 adult patients with active pSS to 1 of 4 arms: placebo, s.c. belimumab, i.v. rituximab, or sequential belimumab + rituximab. RESULTS. Overall, 60 patients completed treatment and follow-up until week 68. The incidence of adverse events (AEs) and drug-related AEs was similar across groups. Infections/infestations were the most common AEs, and no serious infections of special interest occurred. Near-complete depletion of minor salivary gland CD20+ B cells and a greater and more sustained depletion of peripheral CD19+ B cells were observed with belimumab + rituximab versus monotherapies. With belimumab + rituximab, reconstitution of peripheral B cells occurred, but it was delayed compared with rituximab. At week 68, mean (± standard error) total EULAR Sjögren's syndrome disease activity index scores decreased from 11.0 (1.17) at baseline to 5.0 (1.27) for belimumab + rituximab and 10.4 (1.36) to 8.6 (1.57) for placebo. CONCLUSION. The safety profile of belimumab + rituximab in pSS was consistent with the monotherapies. Belimumab + rituximab induced enhanced salivary gland B cell depletion relative to the monotherapies, potentially leading to improved clinical outcomes.
Published: 2022

42. Addressing the clinical unmet needs in primary Sjögren’s Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

Author: Pezoulas, Vasileios C, Goules, Andreas, Kalatzis, Fanis, Chatzis, Luke, Kourou, Konstantina D, Venetsanopoulou, Aliki, Exarchos, Themis P, Gandolfo, Saviana, Votis, Konstantinos, Zampeli, Evi, Baurmeister, Jan, Thorsten, May, Pérez, Manuel M, Lishchuk, Iryna, Chondrogiannis, Thymios, Andronikou, Vassiliki, Varvarigou, Theodora, Filipovic, Nenad, Tsiknakis, Manolis, Baldini, Chiara, Bombardieri, Michele, Bootsma, Hendrika, Bowman, Simon, Soyfoo, Muhammad Shahnawaz, Parisis, Dorian, Delporte, Christine, Devauchelle-Pensec, Valérie, Pers, Jacques-Olivier, Dörner, Thomas, Bartolini, Elena, Gerli, Roberto, Giacomelli, Roberto, Johnsson, Roland, Ng, Wan-Fai, Priori, Roberta, Casals, Manuel Ramos, Sivils, Kathy, Skopouli, Fotini, Witte, Torsten, Van Roon, Joel AG, Mariette, Xavier, De Vita, Salvatore, Tzioufas, Athanasios, Fotiadis, Dimitrios Ioannis, Pezoulas, Vasileios C, Goules, Andreas, Kalatzis, Fanis, Chatzis, Luke, Kourou, Konstantina D, Venetsanopoulou, Aliki, Exarchos, Themis P, Gandolfo, Saviana, Votis, Konstantinos, Zampeli, Evi, Baurmeister, Jan, Thorsten, May, Pérez, Manuel M, Lishchuk, Iryna, Chondrogiannis, Thymios, Andronikou, Vassiliki, Varvarigou, Theodora, Filipovic, Nenad, Tsiknakis, Manolis, Baldini, Chiara, Bombardieri, Michele, Bootsma, Hendrika, Bowman, Simon, Soyfoo, Muhammad Shahnawaz, Parisis, Dorian, Delporte, Christine, Devauchelle-Pensec, Valérie, Pers, Jacques-Olivier, Dörner, Thomas, Bartolini, Elena, Gerli, Roberto, Giacomelli, Roberto, Johnsson, Roland, Ng, Wan-Fai, Priori, Roberta, Casals, Manuel Ramos, Sivils, Kathy, Skopouli, Fotini, Witte, Torsten, Van Roon, Joel AG, Mariette, Xavier, De Vita, Salvatore, Tzioufas, Athanasios, and Fotiadis, Dimitrios Ioannis
Abstract: info:eu-repo/semantics/published
Published: 2022

43. CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi, Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi, Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases., CC BY 4.0Contact Sandra Hellberg Email iconsandra.hellberg@liu.sePublished online: 04 Oct 2021Copyright © 2022 Informa UK Limited This work was supported by the Swedish Foundation for Strategic Research (SB16-0011), Swedish Research Council (K2013-61X-22310-01-4, 2015-030807, 2018-02776) and Lions research grant (Liu-2012-01948).
Published: 2022
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44. CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi, Hellberg, Sandra, Bhai Mehta, Ratnesh, Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm, Benson, Mikael, Berg, Göran, Jenmalm, Maria, Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi, Hellberg, Sandra, Bhai Mehta, Ratnesh, Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm, Benson, Mikael, Berg, Göran, Jenmalm, Maria, Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases., Funding Agencies|Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [SB16-0011]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [K2013-61X-22310-01-4, 2015-030807, 2018-02776]; Lions research grant [Liu-2012-01948]
Published: 2022
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45. CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi, Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi, Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases., CC BY 4.0Contact Sandra Hellberg Email iconsandra.hellberg@liu.sePublished online: 04 Oct 2021Copyright © 2022 Informa UK Limited This work was supported by the Swedish Foundation for Strategic Research (SB16-0011), Swedish Research Council (K2013-61X-22310-01-4, 2015-030807, 2018-02776) and Lions research grant (Liu-2012-01948).
Published: 2022
Full Text: View/download PDF

46. CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi, Hellberg, Sandra, Bhai Mehta, Ratnesh, Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm, Benson, Mikael, Berg, Göran, Jenmalm, Maria, Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi, Hellberg, Sandra, Bhai Mehta, Ratnesh, Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm, Benson, Mikael, Berg, Göran, Jenmalm, Maria, Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases., Funding Agencies|Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [SB16-0011]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [K2013-61X-22310-01-4, 2015-030807, 2018-02776]; Lions research grant [Liu-2012-01948]
Published: 2022
Full Text: View/download PDF

47. CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi, Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi, Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases., CC BY 4.0Contact Sandra Hellberg Email iconsandra.hellberg@liu.sePublished online: 04 Oct 2021Copyright © 2022 Informa UK Limited This work was supported by the Swedish Foundation for Strategic Research (SB16-0011), Swedish Research Council (K2013-61X-22310-01-4, 2015-030807, 2018-02776) and Lions research grant (Liu-2012-01948).
Published: 2022
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48. The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET

Author: Talarico, Rosaria, Aguilera, Silvia, Alexander, Tobias, Amoura, Zahir, Antunes, Ana M., Arnaud, Laurent, Avcin, Tadej, Beretta, Lorenzo, Bombardieri, Stefano, Burmester, Gerd R., Cannizzo, Sara, Cavagna, Lorenzo, Chaigne, Benjamin, Cornet, Alain, Costedoat-Chalumeau, Nathalie, Doria, Andrea, Ferraris, Alessandro, Fischer-Betz, Rebecca, Fonseca, Joao E., Frank, Charissa, Gaglioti, Andrea, Galetti, Ilaria, Grunert, Juergen, Guimaraes, Vera, Hachulla, Eric, Houssiau, Frederic, Iaccarino, Luca, Krieg, Thomas, Limper, Marteen, Malfait, Fransiska, Mariette, Xavier, Marinello, Diana, Martin, Thierry, Matthews, Lisa, Matucci-Cerinic, Marco, Meyer, Alain, Montecucco, Carlomaurizio, Mouthon, Luc, Mueller-Ladner, Ulf, Rednic, Simona, Romao, Vasco C., Schneider, Matthias, Smith, Vanessa, Sulli, Alberto, Tamirou, Farah, Taruscio, Domenica, Taulaigo, Anna V., Terol, Enrique, Tincani, Angela, Ticciati, Simone, Turchetti, Giuseppe, van Hagen, P. Martin, van Laar, Jacob M., Vieira, Ana, de Vries-Bouwstra, Jeska K., Cutolo, Maurizio, Mosca, Marta, Talarico, Rosaria, Aguilera, Silvia, Alexander, Tobias, Amoura, Zahir, Antunes, Ana M., Arnaud, Laurent, Avcin, Tadej, Beretta, Lorenzo, Bombardieri, Stefano, Burmester, Gerd R., Cannizzo, Sara, Cavagna, Lorenzo, Chaigne, Benjamin, Cornet, Alain, Costedoat-Chalumeau, Nathalie, Doria, Andrea, Ferraris, Alessandro, Fischer-Betz, Rebecca, Fonseca, Joao E., Frank, Charissa, Gaglioti, Andrea, Galetti, Ilaria, Grunert, Juergen, Guimaraes, Vera, Hachulla, Eric, Houssiau, Frederic, Iaccarino, Luca, Krieg, Thomas, Limper, Marteen, Malfait, Fransiska, Mariette, Xavier, Marinello, Diana, Martin, Thierry, Matthews, Lisa, Matucci-Cerinic, Marco, Meyer, Alain, Montecucco, Carlomaurizio, Mouthon, Luc, Mueller-Ladner, Ulf, Rednic, Simona, Romao, Vasco C., Schneider, Matthias, Smith, Vanessa, Sulli, Alberto, Tamirou, Farah, Taruscio, Domenica, Taulaigo, Anna V., Terol, Enrique, Tincani, Angela, Ticciati, Simone, Turchetti, Giuseppe, van Hagen, P. Martin, van Laar, Jacob M., Vieira, Ana, de Vries-Bouwstra, Jeska K., Cutolo, Maurizio, and Mosca, Marta
Abstract: During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.
Published: 2021

49. CD4+ T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Author: Badam, Tejaswi V., Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, Ernerudh, Jan, Badam, Tejaswi V., Hellberg, Sandra, Mehta, Ratnesh B., Lechner-Scott, Jeannette, Lea, Rodney A., Tost, Jorg, Mariette, Xavier, Svensson-Arvelund, Judit, Nestor, Colm E., Benson, Mikael, Berg, Göran, Jenmalm, Maria C., Gustafsson, Mika, and Ernerudh, Jan
Abstract: Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4+ T-cells in non-pregnant and pregnant women, during the 1st and 2nd trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2nd trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases. Abbreviations: BMIQ: beta-mixture quantile dilation; DMGs: differentially methylated genes
Published: 2021

50. The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET.

Author: UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Talarico, Rosaria, Aguilera, Silvia, Alexander, Tobias, Amoura, Zahir, Antunes, Ana M, Arnaud, Laurent, Avcin, Tadej, Beretta, Lorenzo, Bombardieri, Stefano, Burmester, Gerd R, Cannizzo, Sara, Cavagna, Lorenzo, Chaigne, Benjamin, Cornet, Alain, Costedoat-Chalumeau, Nathalie, Doria, Andrea, Ferraris, Alessandro, Fischer-Betz, Rebecca, Fonseca, João E, Frank, Charissa, Gaglioti, Andrea, Galetti, Ilaria, Grunert, Jürgen, Guimarães, Vera, Hachulla, Eric, Houssiau, Frédéric, Iaccarino, Luca, Krieg, Thomas, Limper, Marteen, Malfait, Fransiska, Mariette, Xavier, Marinello, Diana, Martin, Thierry, Matthews, Lisa, Matucci-Cerinic, Marco, Meyer, Alain, Montecucco, Carlomaurizio, Mouthon, Luc, Müller-Ladner, Ulf, Rednic, Simona, Romão, Vasco C, Schneider, Matthias, Smith, Vanessa, Sulli, Alberto, Tamirou, Farah, Taruscio, Domenica, Taulaigo, Anna V, Terol, Enrique, Tincani, Angela, Ticciati, Simone, Turchetti, Giuseppe, van Hagen, P Martin, van Laar, Jacob M, Vieira, Ana, de Vries-Bouwstra, Jeska K, Cutolo, Maurizio, Mosca, Marta, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Talarico, Rosaria, Aguilera, Silvia, Alexander, Tobias, Amoura, Zahir, Antunes, Ana M, Arnaud, Laurent, Avcin, Tadej, Beretta, Lorenzo, Bombardieri, Stefano, Burmester, Gerd R, Cannizzo, Sara, Cavagna, Lorenzo, Chaigne, Benjamin, Cornet, Alain, Costedoat-Chalumeau, Nathalie, Doria, Andrea, Ferraris, Alessandro, Fischer-Betz, Rebecca, Fonseca, João E, Frank, Charissa, Gaglioti, Andrea, Galetti, Ilaria, Grunert, Jürgen, Guimarães, Vera, Hachulla, Eric, Houssiau, Frédéric, Iaccarino, Luca, Krieg, Thomas, Limper, Marteen, Malfait, Fransiska, Mariette, Xavier, Marinello, Diana, Martin, Thierry, Matthews, Lisa, Matucci-Cerinic, Marco, Meyer, Alain, Montecucco, Carlomaurizio, Mouthon, Luc, Müller-Ladner, Ulf, Rednic, Simona, Romão, Vasco C, Schneider, Matthias, Smith, Vanessa, Sulli, Alberto, Tamirou, Farah, Taruscio, Domenica, Taulaigo, Anna V, Terol, Enrique, Tincani, Angela, Ticciati, Simone, Turchetti, Giuseppe, van Hagen, P Martin, van Laar, Jacob M, Vieira, Ana, de Vries-Bouwstra, Jeska K, Cutolo, Maurizio, and Mosca, Marta
Abstract: During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.
Published: 2021

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