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2. The enigma of sclera-specific autoimmunity in scleritis

Author

Vergouwen, Daphne P.C., van Beek, Adriaan A., de Hoog, Joeri, de Boer, Joke H., Los, Leonoor I., Gijs, Marlies, Erckens, Roel J., Verdijk, Rob M., Haasnoot, Geert W., Roelen, Dave L., Rothova, Aniki, Rönnelid, Johan, Ten Berge, Josianne C., and Schreurs, Marco W.J.

Published
2024
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7. Exhaled Nitric Oxide Reflects the Immune Reactions of the Airways in Early Rheumatoid Arthritis.

Author

Weitoft, Tomas, Rönnelid, Johan, Lind, Anders, de Vries, Charlotte, Larsson, Anders, Potempa, Barbara, Potempa, Jan, Kastbom, Alf, Martinsson, Klara, Lundberg, Karin, and Högman, Marieann

Subjects
NITRIC oxide, RHEUMATOID factor, PEPTIDES, C-reactive protein, PORPHYROMONAS gingivalis, RHEUMATOID arthritis
Abstract

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman–Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against Porphyromonas gingivalis (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho −0.48, p = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho −0.41, p = 0.017), between the alveolar concentration and free secretory component (Rho −0.35, p = 0.023) and between the alveolar concentration and C-reactive protein (Rho −0.36, p = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Correction to: The citrullinated/native index of autoantibodies against hnRNP-DL predicts an individual “window of treatment success” in RA patients

Author

Marklein, Bianka, Jenning, Madeleine, Konthur, Zoltán, Häupl, Thomas, Welzel, Franziska, Nonhoff, Ute, Krobitsch, Sylvia, Mulder, Debbie M., Koenders, Marije I., Joshua, Vijay, Cope, Andrew P., Shlomchik, Mark J., Anders, Hans-Joachim, Burmester, Gerd R., Hensvold, Aase, Catrina, Anca I., Rönnelid, Johan, Steiner, Günter, and Skriner, Karl

Published
2021
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9. The citrullinated/native index of autoantibodies against hnRNP-DL predicts an individual “window of treatment success” in RA patients

Author

Marklein, Bianka, Jenning, Madeleine, Konthur, Zoltán, Häupl, Thomas, Welzel, Franziska, Nonhoff, Ute, Krobitsch, Sylvia, Mulder, Debbie M., Koenders, Marije I., Joshua, Vijay, Cope, Andrew P., Shlomchik, Mark J., Anders, Hans-Joachim, Burmester, Gerd R., Hensvold, Aase, Catrina, Anca I., Rönnelid, Johan, Steiner, Günter, and Skriner, Karl

Published
2021
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10. Distinct HLA Associations with Rheumatoid Arthritis Subsets Defined by Serological Subphenotype

Author

Terao, Chikashi, Brynedal, Boel, Chen, Zuomei, Jiang, Xia, Westerlind, Helga, Hansson, Monika, Jakobsson, Per-Johan, Lundberg, Karin, Skriner, Karl, Serre, Guy, Rönnelid, Johan, Mathsson-Alm, Linda, Brink, Mikael, Dahlqvist, Solbritt Rantapää, Padyukov, Leonid, Gregersen, Peter K., Barton, Anne, Alfredsson, Lars, Klareskog, Lars, and Raychaudhuri, Soumya

Published
2019
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11. In early rheumatoid arthritis, anticitrullinated peptide antibodies associate with low number of affected joints and rheumatoid factor associates with systemic inflammation.

Author

Pertsinidou, Eleftheria, Saevarsdottir, Saedis, Manivel, Vivek Anand, Klareskog, Lars, Alfredsson, Lars, Mathsson-Alm, Linda, Hansson, Monika, Cornillet, Martin, Serre, Guy, Holmdahl, Rikard, Skriner, Karl, Jakobsson, Per-Johan, Westerlind, Helga, Askling, Johan, and Rönnelid, Johan

Published
2024
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21. The EuroMyositis registry: an international collaborative tool to facilitate myositis research

Author

Lilleker, James B, Vencovsky, Jiri, Wang, Guochun, Wedderburn, Lucy R, Diederichsen, Louise Pyndt, Schmidt, Jens, Oakley, Paula, Benveniste, Olivier, Danieli, Maria Giovanna, Danko, Katalin, Thuy, Nguyen Thi Phuong, Vazquez-Del Mercado, Monica, Andersson, Helena, De Paepe, Boel, deBleecker, Jan L, Maurer, Britta, McCann, Liza J, Pipitone, Nicolo, McHugh, Neil, Betteridge, Zoe E, New, Paul, Cooper, Robert G, Ollier, William E, Lamb, Janine A, Krogh, Niels Steen, Lundberg, Ingrid E, Chinoy, Hector, D’hose, Sophie, Tian, Xin Lu,xiaolan, Mann, Herman, Kryštufková, Olga, Pleštilová, Lenka, Barochová,katerina kubínová, Martin Klein,tereza, Gelardi, Chiara, Pedini, Veronica, Cardinaletti, Paolo, Jara, Luis J, Saavedra, Miguel A, Cruz-reyes, Claudia V, Vera-lastra, Olga, Andrade-ortega, Lilia, Medrano-ramírez, Gabriel, Satoh, Minoru, Salazar-páramo, Mario, Gomez-bañuelos, Eduardo, Aguilar-arreola, Jorge, Durán-barragán, Sergio, Navarro-hernandez, Rosa Elena, Petri, Marcelo H, Molberg, Øyvind, Dastmalchi, Maryam, Notarnicola, Antonella, Gheorghe, Karina, Rönnelid, Johan, Liden, Maria, Hanna, Balsam, Jalal, Awat, Hellström, Helena, Martineus, Jehns Christian, Ngoc lan, Nguyen Thi, Padyukov, Leonid, New, Paul, Platt, Hazel, Rothwell, Simon, Ahmed, Yasmeen, Armstrong, Raymond, Bernstein, Robert, Black, Carol, Bowman, Simon, Bruce, Ian, Butler, Robin, Carty, John, Chattopadhyay, Chandra, Chelliah, Easwaradhas, Clarke, Fiona, Dawes, Peter, Denton, Christopher, Devlin, Joseph, Edwards, Christopher, Emery, Paul, Fordham, John, Fraser, Alexander, Gaston, Hill, Gordon, Patrick, Griffiths, Bridget, Gunawardena, Harsha, Hall, Frances, Hanna, Michael, Harrison, Beverley, Hay, Elaine, Hilton-jones, David, Horden, Lesley, Isaacs, John, Isenberg, David, Jones, Adrian, Kamath, Sanjeet, Kennedy, Thomas, Kitas, George, Klimiuk, Peter, Knights, Sally, Lambert, John, Lanyon, Peter, Laxminarayan, Ramasharan, Lecky, Bryan, Luqmani, Raashid, Machado, Pedro, Marks, Jeffrey, Martin, Michael, Mcgonagle, Dennis, Mchugh, Neil, Mckenna, Francis, Mclaren, John, Mcmahon, Michael, Mcrorie, Euan, Merry, Peter, Miles, Sarah, Miller, James, Nicholls, Anne, Nixon, Jennifer, Ong, Voon, Over, Katherine, Packham, John, Pipitone, Nicolo, Plant, Michael, Pountain, Gillian, Pullar, Thomas, Roberts, Mark, Sanders, Paul, Scott, David, Scott, David, Shadforth, Michael, Sheeran, Thomas, Srinivasan, Arul, Swinson, David, Teh, Lee-suan, Webley, Michael, Williams, Brian, and Winer, Jonathan

Published
2018
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23. Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1

Author

Eriksson, Daniel, Dalin, Frida, Eriksson, Gabriel Nordling, Landegren, Nils, Bianchi, Matteo, Hallgren, Åsa, Dahlqvist, Per, Wahlberg, Jeanette, Ekwall, Olov, Winqvist, Ola, Catrina, Sergiu-Bogdan, Rönnelid, Johan, Hulting, Anna-Lena, Lindblad-Toh, Kerstin, Alimohammadi, Mohammad, Husebye, Eystein S, Knappskog, Per Morten, Rosengren Pielberg, Gerli, Bensing, Sophie, Kämpe, Olle, Bensing, Sophie, Hulting, Anna-Lena, Ekwall, Olov, Dahlqvist, Per, Wahlberg, Jeanette, Olsson, Tommy, Kriström, Berit, Laudius, Maria, Kämpe, Olle, Isaksson, Magnus, Stenlid, Maria Halldin, Gustafsson, Jan, Gebre-Medhin, Gennet, Björnsdottir, Sigridur, Eriksson, Gabriel-Nordling, Janson, Annika, Åkerman, Anna-Karin, Bergthorsdottir, Ragnhildur, Johannsson, Gudmundur, Lindskog, Emma, Elfving, Maria, Waldenström, Erik, Svensson, Johan, Kalcheva, Zlatka, Eliasson, Mats, Hedman, Erik, Wahlin, Karin, Magnusson, Anders, Ekman, Bertil, and Munoz, Karel Duchen

Published
2018

24. The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis.

Author

Westerlind, Helga, Kastbom, Alf, Rönnelid, Johan, Hansson, Monika, Alfredsson, Lars, Mathsson-Alm, Linda, Serre, Guy, Cornillet, Martin, Holmdahl, Rikard, Skriner, Karl, Bang, Holger, Klareskog, Lars, Saevarsdottir, Saedis, Lundberg, Karin, Grönwall, Caroline, and Askling, Johan

Subjects
THROMBOEMBOLISM risk factors, PROTEIN metabolism, CARDIOVASCULAR diseases risk factors, AUTOANTIBODIES, VEINS, CONFIDENCE intervals, IMMUNOGLOBULINS, HLA-B27 antigen, RISK assessment, COMPARATIVE studies, RHEUMATOID arthritis, FIBRINOGEN, THROMBOEMBOLISM, DESCRIPTIVE statistics, RESEARCH funding, LONGITUDINAL method, PROPORTIONAL hazards models, DISEASE complications
Abstract

Objectives To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from RA diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein modifications, in particular recognizing citrullination (e.g. citrullinated fibrinogen) and RF by isotype. Methods A cohort of 2814 patients with newly diagnosed RA were followed for incident VTE through register linkages. Sera from RA diagnosis were centrally analysed for antibodies to second generation cyclic citrullinated peptides (anti-CCP2), 20 anti-citrullinated protein antibody (ACPA) fine-specificities, antibodies to additional protein modifications (carbamylation and acetylation) and RF by isotype. Association between baseline serology status and future VTE was analysed using Cox regression adjusted for age, sex and calendar period of RA diagnosis, overall and stratified by anti-CCP2 and RF positivity. Results During a median 16 years of follow-up, 213 first-ever VTE events were registered (5.0/1000 person-years). IgG anti-CCP2 (present in 65% of cohort) associated with VTE (hazard ratio [HR] = 1.33, 95% CI: 1.00, 1.78), in a dose-response manner. The risk of VTE increased with number of ACPA fine-specificities. IgM RF, but no other RF isotypes, associated with VTE (HR = 1.38, 95% CI: 1.04, 1.82). The associations were independent from smoking and HLA-DRB1 shared epitope alleles. None of the carbamylated or acetylated antibody reactivities associated with VTE. Conclusion Anti-CCP2, load of ACPA fine-specificities and IgM RF at RA diagnosis are associated with an increased risk of future VTE in RA. Antibodies to citrullinated fibrinogen did not differ substantially from other ACPA fine-specificities. Autoreactivity to other post-translational modifications was not associated with VTE risk. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Clinical and Immunological Characteristics of Autoimmune Addison Disease: A Nationwide Swedish Multicenter Study

Author

Dalin, Frida, Nordling Eriksson, Gabriel, Dahlqvist, Per, Hallgren, Åsa, Wahlberg, Jeanette, Ekwall, Olov, Söderberg, Stefan, Rönnelid, Johan, Olcén, Per, Winqvist, Ola, Catrina, Sergiu-Bogdan, Kriström, Berit, Laudius, Maria, Isaksson, Magnus, Halldin Stenlid, Maria, Gustafsson, Jan, Gebre-Medhin, Gennet, Björnsdottir, Sigridur, Janson, Annika, Åkerman, Anna-Karin, Åman, Jan, Duchen, Karel, Bergthorsdottir, Ragnhildur, Johannsson, Gudmundur, Lindskog, Emma, Landin-Olsson, Mona, Elfving, Maria, Waldenström, Erik, Hulting, Anna-Lena, Kämpe, Olle, and Bensing, Sophie

Published
2017

31. Anti-phosphatidylserine/prothrombin antibodies and thrombosis associate positively with HLA-DRB1*13 and negatively with HLA-DRB1*03 in SLE.

Author

Elbagir, Sahwa, Diaz-Gallo, Lina-Marcela, Grosso, Giorgia, Zickert, Agneta, Gunnarsson, Iva, Mahler, Michael, Svenungsson, Elisabet, and Rönnelid, Johan

Subjects
THROMBOSIS risk factors, THROMBOSIS prevention, AUTOANTIBODIES, THROMBOSIS, CARDIOVASCULAR diseases risk factors, STATISTICS, TRIGLYCERIDES, HLA-B27 antigen, ANTIPHOSPHOLIPID syndrome, MULTIVARIATE analysis, PROTHROMBIN, ALLELES, RISK assessment, COMPARATIVE studies, RESEARCH funding, DESCRIPTIVE statistics, PHOSPHOLIPIDS, SYSTEMIC lupus erythematosus, ODDS ratio, HIGH density lipoproteins, LIPIDS, DISEASE risk factors
Abstract

Objectives Emerging evidence demonstrates that aPS-PT associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional aPL [anti-β2glycoprotein-I (anti-β2GPI) and aCL]. We investigated associations between aPS-PT and HLA-DRB1 * alleles and thrombosis in SLE. Conventional aPL were included for comparison. Methods We included 341 consecutive SLE patients, with information on general cardiovascular risk factors, including blood lipids, LA and thrombotic events. aPS/PT, anti-β2GPI and aCL of IgA/G/M isotypes and LA were quantified. Results aPS/PT antibodies associated positively with HLA-DRB1 *13 [odds ratio (OR) 2.7, P  = 0.002], whereas anti-β2GPI and aCL antibodies associated primarily with HLA-DRB1*04 (OR 2.5, P  = 0.0005). These associations remained after adjustment for age, gender and other HLA-DRB1 * alleles. HLA-DRB1*13 , but not DRB1*04 , remained as an independent risk factor for thrombosis and APS after adjustment for aPL and cardiovascular risk factors. The association between DRB1*13 and thrombosis was mediated by aPS-PT positivity. HLA-DRB1*03 , on the other hand, associated negatively with thrombotic events as well as all aPL using both uni- and multivariate analyses. HLA-DRB1*03 had a thrombo-protective effect in aPL-positive patients. Additionally, HLA-DRB1*03 was associated with a favourable lipid profile regarding high-density lipoprotein and triglycerides. Conclusions HLA-DRB1*13 confers risk for both aPS-PT and thrombotic events in lupus. The association between HLA-DRB1*13 and thrombosis is largely, but not totally, mediated through aPS-PT. HLA-DRB1*03 was negatively associated with aPL and positively with favourable lipid levels. Thus, HLA-DRB1*03 seems to identify a subgroup of SLE patients with reduced vascular risk. [ABSTRACT FROM AUTHOR]

Published
2023
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34. ELISA, protein immunoprecipitation and line blot assays for anti-TIF1-gamma autoantibody detection in cancer-associated dermatomyositis.

Author

Selickaja, Sandra, Galindo-Feria, Angeles S, Dani, Lara, Mimori, Tsuneyo, Rönnelid, Johan, Holmqvist, Marie, Lundberg, Ingrid E, and Venalis, Paulius

Subjects
TUMOR risk factors, TUMOR diagnosis, AUTOANTIBODIES, NUCLEOTIDE separation, REPORTING of diseases, DERMATOMYOSITIS, PREDICTIVE tests, PRECIPITIN tests, IMMUNOBLOTTING, RISK assessment, COMPARATIVE studies, ENZYME-linked immunosorbent assay, DESCRIPTIVE statistics, SENSITIVITY & specificity (Statistics), DISEASE complications
Abstract

Objectives Anti‐TIF1-gamma autoantibodies can be detected with immunoprecipitation (IP), line blot (LB) and ELISA. We compared assay performance in patients with DM and the potential of these assays to detect anti-TIF1-gamma positive cancer-associated DM (CADM). Methods We included sera from 131 patients with DM followed at Karolinska University Hospital, Stockholm, Sweden and 82 healthy controls. Serum samples taken at DM diagnosis were tested for anti-TIF1-gamma autoantibodies with IP, two ELISAs (in-house and commercial) and LB. Cancer diagnosis and dates were obtained from the Swedish national cancer register. CADM was defined as a malignancy that developed within 3 years of DM diagnosis. Results Anti-TIF1-gamma autoantibodies were detected in 19/101 (18.8%), 15/113 (13.2%), 34/131 (26%) and 45/131 (34.4%) of the patients with IP, LB, in-house and commercial ELISA, respectively. The anti-TIF1-gamma results from the in-house ELISA were confirmed with IP in 93 of 101 (92%) cases, κ = 0.76, with a commercial ELISA in 110 of 131 (84%) cases, κ = 0.63, and with LB in 101 of 113 (89.3%) cases, κ = 0.67. Anti-TIF1-gamma results with IP were confirmed with LB in 85 of 92 (92.4%) cases, κ = 0.73. For detecting CADM, the anti-TIF1-gamma in-house ELISA had a sensitivity of 58% and specificity of 86%, the commercial ELISA had a sensitivity of 63% and specificity of 82%, IP had a sensitivity of 52% and specificity of 92%, LB had a sensitivity of 40% and specificity of 96%. Conclusion The two anti-TIF1-gamma ELISA assays had advantages both for autoantibody detection and to identify anti-TIF1-gamma-positive CADM. [ABSTRACT FROM AUTHOR]

Published
2022
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35. Anti-citrullinated protein antibody specificities and pulmonary fibrosis in relation to genetic loci in early rheumatoid arthritis.

Author

Brink, Mikael, Ljung, Lotta, Hansson, Monika, Rönnelid, Johan, Holmdahl, Rickard, Skriner, Karl, Serre, Guy, Klareskog, Lars, and Rantapää-Dahlqvist, Solbritt

Subjects
AUTOANTIBODIES, RESEARCH, CONFIDENCE intervals, GENETIC testing, RISK assessment, RHEUMATOID arthritis, GENOTYPES, DESCRIPTIVE statistics, RESEARCH funding, PULMONARY fibrosis, DATA analysis software, LOGISTIC regression analysis, DISEASE risk factors, DISEASE complications
Abstract

Objectives Pulmonary manifestations in RA are common comorbidities, but the underlying mechanisms are largely unknown. The added value of a multiplex of ACPA and genetic risk markers was evaluated for the development of pulmonary fibrosis (PF) in an inception cohort. Methods A total of 1184 patients with early RA were consecutively included and followed prospectively from the index date until death or 31 December 2016. The presence of 21 ACPA fine specificities was analysed using a custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden). Three SNPs, previously found related to PF were evaluated, rs2609255 (FAM13A), rs111521887 (TOLLIP) and rs35705950 (MUC5B). ACPA and genetic data were available for 841 RA patients, of whom 50 developed radiologically defined PF. Results In unadjusted analyses, 11 ACPA specificities were associated with PF development. In multiple variable analyses, six ACPA specificities were associated with increased risk of PF: vimentin (Vim)60–75, fibrinogen (Fib)β62–78 (72), Fibα621–635, Bla26, collagen (C)II359–369 and F4-CIT-R (P  < 0.01 to P  < 0.05). The number of ACPA specificities was also related to PF development (P  < 0.05 crude and adjusted models). In multiple variable models respectively adjusted for each of the SNPs, the number of ACPA specificities (P  < 0.05 in all models), anti-Vim60–75 (P  < 0.05, in all models), anti-Fibβ62–78 (72) (P  < 0.001 to P  < 0.05), anti-CII359–369 (P  < 0.05 in all models) and anti-F4-CIT-R AQ4 (P  < 0.01 to P  < 0.05), anti-Fibα621–635 (P  < 0.05 in one) and anti-Bla26 (P  < 0.05 in two) were significantly associated with PF development. Conclusion The development of PF in an inception cohort of RA patients was associated with both presence of certain ACPA and the number of ACPA specificities and risk genes. [ABSTRACT FROM AUTHOR]

Published
2022
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40. False Positive Results in SARS-CoV-2 Serological Tests for Samples From Patients With Chronic Inflammatory Diseases

Author

Kharlamova, Nastya, Dunn, Nicky, Bedri, Sahl K., Jerling, Svante, Almgren, Malin, Faustini, Francesca, Gunnarsson, Iva, Rönnelid, Johan, Pullerits, Rille, Gjertsson, Inger, Lundberg, Karin, Månberg, Anna, Pin, Elisa, Nilsson, Peter, Hober, Sophia, Fink, Katharina, and Fogdell-Hahn, Anna

Subjects
rheumatoid arthritis, Reumatologi och inflammation, systemic lupus erythematosus, SARS-CoV-2, autoantibodies, Immunologi inom det medicinska området, autoimmunity, diagnostics, Immunology in the medical area, skin and connective tissue diseases, multiple sclerosis, rheumatoid factor, Rheumatology and Autoimmunity
Abstract

Patients with chronic inflammatory diseases are often treated with immunosuppressants and therefore are of particular concern during the SARS-CoV-2 pandemic. Serological tests will improve our understanding of the infection and immunity in this population, unless they tests give false positive results. The aim of this study was to evaluate the specificity of SARS-Cov-2 serological assays using samples from patients with chronic inflammatory diseases collected prior to April 2019, thus defined as negative. Samples from patients with multiple sclerosis (MS, n=10), rheumatoid arthritis (RA, n=47) with or without rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (anti-CCP2) and systemic lupus erythematosus (SLE, n=10) with or without RF, were analyzed for SARS-CoV-2 antibodies using 17 commercially available lateral flow assays (LFA), two ELISA kits and one in-house developed IgG multiplex bead-based assay. Six LFA and the in-house validated IgG assay correctly produced negative results for all samples. However, the majority of assays (n=13), gave false positive signal for samples from patients with RA and SLE. This was most notable in samples from RF positive RA patients. No false positive samples were detected in any assay using samples from patients with MS. Poor specificity of commercial serological assays could possibly be, at least partly, due to interfering antibodies in samples from patients with chronic inflammatory diseases. For these patients, the risk of false positivity should be considered when interpreting results of the SARS-CoV-2 serological assays.

Published
2021

44. International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies

Author

Agmon-Levin, Nancy, Damoiseaux, Jan, Kallenberg, Cees, Sack, Ulrich, Witte, Torsten, Herold, Manfred, Bossuyt, Xavier, Musset, Lucille, Cervera, Ricard, Plaza-Lopez, Aresio, Dias, Carlos, Sousa, Maria José, Radice, Antonella, Eriksson, Catharina, Hultgren, Olof, Viander, Markku, Khamashta, Munther, Regenass, Stephan, Andrade, Luis Eduardo Coelho, Wiik, Allan, Tincani, Angela, Rönnelid, Johan, Bloch, Donald B, Fritzler, Marvin J, Chan, Edward K L, Garcia-De La Torre, I, Konstantinov, Konstantin N, Lahita, Robert, Wilson, Merlin, Vainio, Olli, Fabien, Nicole, Sinico, Renato Alberto, Meroni, Pierluigi, Shoenfeld, Yehuda, Tervaert, JW Cohen, Hamann, D, Derksen, RHWM, Hooijkaas, H, Klasen, I, Limburg, P, Smeenk, R, van Daele, P, Elvin, Kerstin, Dahle, Charlotte, Skogh, Thomas, Antonen, Jaakko, Haapala, Anna-Maija, Hietarinta, Marja, Häkkinen, Teija, Hänninen, Arno, Jokiranta, Sakari, Karjalainen, Anna, Laatikainen, Aino, Leirisalo-Repo, Marjatta, Luosujärvi, Riitta, Miettinen, Aaro, Siuro, Jari, Sved, Sune, Tuuminen, Tamara, Walle, Timo, Coelho, Fátima, Santos, Maria José, Bogas, Mónica, Ramos, João P, Faro-Viana, João, Olsson, Nils Olivier, Chyderiotis, Georges, Bach-Nga, Aubert, Vincent, Dahinden, Clemens, Dayer, Eric, Mascart, Françoise, Tomasi, Jean-Paul, Vercammen, Martine, Verschueren, Patrick, Houssiau, Fréderic, Lauwerys, Bernard, De Keyser, Filip, Fierz, Walter, Heijnen, Ingmar, Keller, Franco, Müllner, Gerhard, Regenass, Stephan, Roux-Lombard, Pascale, Wirthmüller, Urs, Gilburde, Boris, Levi, Rachel, Lipinsky, Daphna, Barak, Mira, Mahmud, Abu-Shakra, Fishel, Ruth, Foguel, Mina, Shay, Kivity, Csernok, Elena, Schlüter, Bernhard, Becker, Bettina, Mierau, Rudolf, Witte, Torsten, Seidel, Wolfram, Frank, Ingrid, Kromminga, Arno, Hiepe, Falk, Conrad, Karsten, Sticherling, Michael, Steiner, Guenter, and Valentyna, Chopyak

Published
2014
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45. Autoantibodies Associated with Autoimmune Liver Diseases in a Healthy Population: Evaluation of a Commercial Immunoblot Test.

Author

Ahmad, Awais, Dahle, Charlotte, Rönnelid, Johan, Sjöwall, Christopher, and Kechagias, Stergios

Subjects
CHOLANGITIS, AUTOIMMUNE diseases, AUTOANTIBODIES, LIVER diseases, AUTOIMMUNE hepatitis, LIVER function tests
Abstract

Autoantibodies constitute important tools for diagnosing the autoimmune liver diseases (AILD) autoimmune hepatitis and primary biliary cholangitis. The EUROLINE immunoblot assay, detecting multiple specificities, is widely used, but the clinical importance of weakly positive findings is unclear. The manufacturer's recommended cut-off was evaluated by investigating AILD-associated autoantibodies in 825 blood donors and 60 confirmed AILD cases. Positive findings were followed up with immunofluorescence microscopy on rat tissue, anti-M2-ELISA, alternative immunoblot assay, and liver function tests. Thirty-six (4.4%) blood donors were positive with EUROLINE. The most common specificities were LC-1 (1.6%), gp210 (1.3%), and AMA-M2 (1.1%). In general, the positive results were higher in patients than in blood donors, whereas anti-LC-1 was higher in blood donors. The liver function tests were slightly elevated in 2 of the 36 immunoblot positive blood donors. The majority of the positive EUROLINE findings could not be confirmed with the follow-up tests. The EUROLINE-Autoimmune Liver Diseases-(IgG) immunoblot detected autoantibodies in 4.4% of blood donors without signs of AILD. Our findings indicate that the recommended cut-off can be raised for most specificities without loss of diagnostic sensitivity. The prevalence of anti-LC-1 among blood donors indicates a problem with the antigen source. [ABSTRACT FROM AUTHOR]

Published
2022
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46. Extramucosal Formation and Prognostic Value of Secretory Antibodies in Rheumatoid Arthritis.

Author

Martinsson, Klara, Kling, Lovisa Lyttbacka, Roos‐Ljungberg, Karin, Griazeva, Irina, Samoylovich, Marina, Paul, Stephane, Rönnelid, Johan, Weitoft, Tomas, Wetterö, Jonas, and Kastbom, Alf

Subjects
AUTOANTIBODIES, BIOMARKERS, IMMUNOGLOBULINS, RHEUMATOID arthritis
Abstract

Objective: To investigate levels and possible extramucosal formation of secretory Ig, including anti–citrullinated protein antibodies (ACPAs), in rheumatoid arthritis (RA). Methods: Three patient groups were studied: 1) ACPA‐positive patients with musculoskeletal pain without clinical arthritis, 2) patients with recent‐onset RA, and 3) patients with established RA. In baseline serum samples (groups 1 and 2) and paired synovial fluid samples (group 3), we analyzed total secretory IgA, total secretory IgM, free secretory component (SC), and SC‐containing ACPA. Extramucosal formation of SC‐containing ACPA was investigated by preincubating RA sera and affinity‐purified ACPA with recombinant free SC. Results: Compared to healthy controls, serum levels of total secretory IgA and total secretory IgM were increased both in patients with early RA and at‐risk patients (P < 0.05). Patients with early RA with elevated total secretory Ig had significantly higher disease activity during the 3‐year follow‐up period compared to those without increased levels. At‐risk patients who developed arthritis during follow‐up (39 of 82) had higher baseline total secretory IgA levels compared to those who did not (P = 0.041). In established RA, total secretory IgA and total secretory IgM levels were higher in serum than in synovial fluid (P < 0.0001), but SC‐containing ACPAs adjusted for total secretory Ig concentration were higher in synovial fluid (P < 0.0001). Preincubation with recombinant free SC yielded increased SC‐containing ACPA reactivity in sera as well as in affinity‐purified IgA and IgM ACPA preparations. Conclusion: Circulating secretory Ig are elevated before and at RA onset. In the presence of free SC, secretory Ig may form outside the mucosa, and SC‐containing ACPAs are enriched in RA joints. These findings shed important new light on the mucosal connection in RA development. [ABSTRACT FROM AUTHOR]

Published
2022
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48. Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus

Author

Parodis, Ioannis, Åkerström, Emil, Sjöwall, Christopher, Sohrabian, Azita, Jönsen, Andreas, Gomez, Alvaro, Frodlund, Martina, Zickert, Agneta, Bengtsson, Anders A, Rönnelid, Johan, and Gunnarsson, Iva

Subjects
Adult, Male, autoantibodies, B cells, autoimmunity, biologic therapies, cytokines, immune complexes, systemic lupus erythematosus, Interferon alpha-2, Antibodies, Monoclonal, Humanized, Severity of Illness Index, Article, lcsh:Chemistry, Humans, Lupus Erythematosus, Systemic, lcsh:QH301-705.5, Rheumatology and Autoimmunity, Reumatologi och inflammation, Interleukin-6, Middle Aged, Interleukin-10, Treatment Outcome, lcsh:Biology (General), lcsh:QD1-999, Antibodies, Antinuclear, Female
Abstract

We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay. In patients with detectable levels at baseline, interferon (IFN)-a2 levels were lower at month 6 (median; interquartile range (IQR): 8.9; 1.5-54.9 pg/mL) versus baseline (28.4; 20.9-100.3 pg/mL; p = 0.043). Interleukin (IL)-6 (baseline: 7.1; 2.9-16.1 pg/mL) decreased from month 6 (0.5; 0.5-6.3 pg/mL; p = 0.018) and throughout a 24 month follow-up. IL-10 (baseline: 12.6; 2.8-29.7 pg/mL) showed more rapid decreases from month 3 (1.8; 0.6-9.1 pg/mL; p = 0.003). Levels of anti-dsDNA (p < 0.001), anti-Smith antigen (Sm) (p = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) (p < 0.001), anti-Sm-U1RNP complex (p = 0.028), and anti-ribosomal P (p = 0.012) antibodies decreased from month 3 and remained decreased. Anti-Sm positivity at baseline was associated with higher probability and/or shorter time to achieve sustained SLE responder index-4 response (hazard ratio (HR): 2.52; 95% CI: 1.20-5.29; p = 0.015), independently of other factors. Decline of IL-6 levels through month 3 was greater in responders. In summary, belimumab treatment lowered IFN-a2, IL-6, and IL-10 levels, as well as levels of multiple autoantibodies, however after different time spans. Notably, anti-Sm positivity and early decline in IL-6 levels were associated with favorable treatment outcome. Funding agencies: The Swedish Research Council; Swedish RheumatismAssociation (R-859621; R-862161; R-844801); Professor Nanna Svartz Foundation (2018-00250); Ulla and Roland Gustafsson Foundation (2019-12); King Gustaf V’s 80-year Foundation; Swedish Society of Medicine; Ingegerd Johansson Donation; King Gustaf V and Queen Victoria’s Foundation of Freemasons; Region Östergötland (ALF grants); Region Stockholm; Region Uppsala; Region Skåne; Faculty of Medicine, Lund University; AlfredÖsterlund’s Foundation; Anna-Greta Crafoord Foundation; Greta and Johan Kock’s Foundation; Skåne UniversityHospital; and the Karolinska Institutet Foundations.

Published
2020

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