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1. Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy

Author

T2B! immunity against SARS-CoV-2 study group, Stalman, Eileen W., Wieske, Luuk, Keijser, Jim B.D., van Dam, Koos P.J., Kummer, Laura Y.L., Wilbrink, Maarten F., van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D'Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederique J., Voskuyl, Alexandre E., Broens, Bo, Parra Sanchez, Agner, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Onno Teng, Y. K., van Paassen, Pieter, Busch, Matthias H., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, T2B! immunity against SARS-CoV-2 study group, Stalman, Eileen W., Wieske, Luuk, Keijser, Jim B.D., van Dam, Koos P.J., Kummer, Laura Y.L., Wilbrink, Maarten F., van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D'Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederique J., Voskuyl, Alexandre E., Broens, Bo, Parra Sanchez, Agner, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Onno Teng, Y. K., van Paassen, Pieter, Busch, Matthias H., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, and Keijzer, Sofie

Abstract

Background: Despite impaired humoral response in patients treated with immunosuppressants (ISPs), recent studies found similar severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection compared to controls. One potential explanation is the rapid generation of humoral response on infection, but evidence is lacking. Objectives: We investigated the longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infection in patients with immune-mediated inflammatory diseases (IMIDs) receiving ISP therapy and controls. Methods: As a prospective substudy of the national Target-to-B! (T2B!) consortium, we included IMID patients receiving ISPs therapy and controls who reported SARS-CoV-2 breakthrough infection between July 1, 2021, and April 1, 2022. To get an impression of the dynamics of the antibody repertoire, 3 antibody titers of wild-type RBD, wild-type S, and omicron RBD were measured at 4 time points after SARS-CoV-2 breakthrough infection. Results: We included 302 IMID patients receiving ISPs and 178 controls. Antibody titers increased up to 28 days after breakthrough infection in both groups. However, in IMID patients receiving therapy with anti-CD20 and sphingosine-1 phosphate receptor modulators, antibody titers were considerably lower compared to controls. In the anti-TNF group, we observed slightly lower antibody titers in the early stages and a faster decline of antibodies after infection compared to controls. Breakthrough infections were mostly mild, and hospitalization was required in less than 1% of cases. Conclusions: Most ISPs do not influence the dynamics of the SARS-CoV-2 antibody repertoire and exhibit a rapid recall response with cross-reactive antibody clones toward new virus variants. However, in patients treated with anti-CD20 therapy or sphingosine-1 phosphate receptor modulators, the dynamics were greatly impaired, and to a lesser extent in those who received a

Published
2024

2. Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy

Author

Stalman, Eileen W., Wieske, Luuk, Keijser, Jim B.D., van Dam, Koos P.J., Kummer, Laura Y.L., Wilbrink, Maarten F., van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D'Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederique J., Voskuyl, Alexandre E., Broens, Bo, Parra Sanchez, Agner, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Onno Teng, Y. K., van Paassen, Pieter, Busch, Matthias H., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Cristianawati, Olvi, Jonges, Marcel, Stalman, Eileen W., Wieske, Luuk, Keijser, Jim B.D., van Dam, Koos P.J., Kummer, Laura Y.L., Wilbrink, Maarten F., van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D'Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederique J., Voskuyl, Alexandre E., Broens, Bo, Parra Sanchez, Agner, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Onno Teng, Y. K., van Paassen, Pieter, Busch, Matthias H., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Cristianawati, Olvi, and Jonges, Marcel

Abstract

Background: Despite impaired humoral response in patients treated with immunosuppressants (ISPs), recent studies found similar severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection compared to controls. One potential explanation is the rapid generation of humoral response on infection, but evidence is lacking. Objectives: We investigated the longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infection in patients with immune-mediated inflammatory diseases (IMIDs) receiving ISP therapy and controls. Methods: As a prospective substudy of the national Target-to-B! (T2B!) consortium, we included IMID patients receiving ISPs therapy and controls who reported SARS-CoV-2 breakthrough infection between July 1, 2021, and April 1, 2022. To get an impression of the dynamics of the antibody repertoire, 3 antibody titers of wild-type RBD, wild-type S, and omicron RBD were measured at 4 time points after SARS-CoV-2 breakthrough infection. Results: We included 302 IMID patients receiving ISPs and 178 controls. Antibody titers increased up to 28 days after breakthrough infection in both groups. However, in IMID patients receiving therapy with anti-CD20 and sphingosine-1 phosphate receptor modulators, antibody titers were considerably lower compared to controls. In the anti-TNF group, we observed slightly lower antibody titers in the early stages and a faster decline of antibodies after infection compared to controls. Breakthrough infections were mostly mild, and hospitalization was required in less than 1% of cases. Conclusions: Most ISPs do not influence the dynamics of the SARS-CoV-2 antibody repertoire and exhibit a rapid recall response with cross-reactive antibody clones toward new virus variants. However, in patients treated with anti-CD20 therapy or sphingosine-1 phosphate receptor modulators, the dynamics were greatly impaired, and to a lesser extent in those who received a

Published
2024

3. Treat-to-target in dermatology:A scoping review and International Eczema Council survey on the approach in atopic dermatitis

Author

Renert-Yuval, Yael, Del Duca, Ester, Arents, Bernd, Bissonnette, Robert, Drucker, Aaron M., Flohr, Carsten, Guttman-Yassky, Emma, Hijnen, Dirkjan, Kabashima, Kenji, Leshem, Yael A., Paller, Amy S., Silverberg, Jonathan I., Simpson, Eric L., Spuls, Phyllis, Vestergaard, Christian, Wollenberg, Andreas, Irvine, Alan D., Thyssen, Jacob P., Renert-Yuval, Yael, Del Duca, Ester, Arents, Bernd, Bissonnette, Robert, Drucker, Aaron M., Flohr, Carsten, Guttman-Yassky, Emma, Hijnen, Dirkjan, Kabashima, Kenji, Leshem, Yael A., Paller, Amy S., Silverberg, Jonathan I., Simpson, Eric L., Spuls, Phyllis, Vestergaard, Christian, Wollenberg, Andreas, Irvine, Alan D., and Thyssen, Jacob P.

Abstract

Treat-to-target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer-reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T-related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician- and patient-reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD.

Published
2024

4. Risk factors associated with short-term adverse events after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases

Author

Wieske, Luuk, Kummer, Laura Y.L., van Dam, Koos P.J., Stalman, Eileen W., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, Volkers, Adriaan G., D’Haens, Geert R.A.M., Tas, Sander W., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederike J., Killestein, Joep, van Kempen, Zoé L.E., Voskuyl, Alexandre E., Broens, Bo, Sanchez, Agner Parra, Wolbink, Gertjan, Boekel, Laura, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Cornelia F., Teng, Y. K.Onno, van Paassen, Pieter, Busch, Matthias H., Jallah, B. Papay, Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Rispens, Theo, ten Brinke, Anja, Verstegen, Niels J.M., Zwinderman, Koos A.H., van Ham, SM, Kuijpers, Taco W., Eftimov, Filip, Wieske, Luuk, Kummer, Laura Y.L., van Dam, Koos P.J., Stalman, Eileen W., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, Volkers, Adriaan G., D’Haens, Geert R.A.M., Tas, Sander W., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederike J., Killestein, Joep, van Kempen, Zoé L.E., Voskuyl, Alexandre E., Broens, Bo, Sanchez, Agner Parra, Wolbink, Gertjan, Boekel, Laura, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Cornelia F., Teng, Y. K.Onno, van Paassen, Pieter, Busch, Matthias H., Jallah, B. Papay, Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Rispens, Theo, ten Brinke, Anja, Verstegen, Niels J.M., Zwinderman, Koos A.H., van Ham, SM, Kuijpers, Taco W., and Eftimov, Filip

Abstract

Background: Studies have suggested incremental short-term adverse events (AE) after repeated vaccination. In this report, we assessed occurrence and risk factors for short-term AEs following repeated SARS-CoV-2 vaccination in patients with various immune-mediated inflammatory diseases (IMIDs). Methods: Self-reported daily questionnaires on AEs during the first 7 days after vaccination were obtained of 2259 individuals (2081 patients and 178 controls) participating in an ongoing prospective multicenter cohort study on SARS-CoV-2 vaccination in patients with various IMIDs in the Netherlands (T2B-COVID). Relative risks were calculated for potential risk factors associated with clinically relevant AE (rAE), defined as AE lasting longer than 2 days or impacting daily life. Results: In total, 5454 vaccinations were recorded (1737 first, 1992 second and 1478 third vaccinations). Multiple sclerosis, Crohn’s disease and rheumatoid arthritis were the largest disease groups. rAEs were reported by 57.3% (95% CI 54.8–59.8) of patients after the first vaccination, 61.5% (95% CI 59.2–63.7) after the second vaccination and 58% (95% CI 55.3–60.6) after the third vaccination. At day 7 after the first, second and third vaccination, respectively, 7.6% (95% CI 6.3–9.1), 7.4% (95% CI 6.2–8.7) and 6.8% (95% CI 5.4–8.3) of patients still reported AEs impacting daily life. Hospital admissions and allergic reactions were uncommon (<0.7%). Female sex (aRR 1.43, 95% CI 1.32–1.56), age below 50 (aRR 1.14, 95% CI 1.06–1.23), a preceding SARS-CoV-2 infection (aRR 1.14, 95% CI 1.01–1.29) and having an IMID (aRR 1.16, 95% CI 1.01–1.34) were associated with increased risk of rAEs following a vaccination. Compared to the second vaccination, the first vaccination was associated with a lower risk of rAEs (aRR 0.92, 95% CI 0.84–0.99) while a third vaccination was not associated with increased risk on rAEs (aRR 0.93, 95% CI 0.84–1.02). BNT162b2 vaccines were associated with lower risk on rAEs compa

Published
2022

6. EASI p-EASI: Predicting disease severity in atopic dermatitis patients treated with dupilumab using a combination of serum biomarkers

Author

MS Dermatologie/Allergologie, Infection & Immunity, Unit Opleiding Dermatologie, CTI UDAIR, CTI, CTI Research, CDL Patiëntenzorg MI, Cancer, CTI Borghans, Bakker, Daphne S, Ariens, Lieneke F M, Giovannone, Barbara, Hijnen, DirkJan, Delemarre, Eveline M, Knol, Edward, Nierkens, Stefan, de Bruin-Weller, Marjolein S, Thijs, Judith L, Drylewicz, Julia, MS Dermatologie/Allergologie, Infection & Immunity, Unit Opleiding Dermatologie, CTI UDAIR, CTI, CTI Research, CDL Patiëntenzorg MI, Cancer, CTI Borghans, Bakker, Daphne S, Ariens, Lieneke F M, Giovannone, Barbara, Hijnen, DirkJan, Delemarre, Eveline M, Knol, Edward, Nierkens, Stefan, de Bruin-Weller, Marjolein S, Thijs, Judith L, and Drylewicz, Julia

Published
2020

7. PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation

Author

Petrelli, Alessandra, Mijnheer, Gerdien, Hoytema Van Konijnenburg, David P., Van Der Wal, Maria M., Giovannone, Barbara, Mocholi, Enric, Vazirpanah, Nadia, Broen, Jasper C., Hijnen, Dirkjan, Oldenburg, Bas, Coffer, Paul J., Vastert, Sebastian J., Prakken, Berent J., Spierings, Eric, Pandit, Aridaman, Mokry, Michal, Van Wijk, Femke, Petrelli, Alessandra, Mijnheer, Gerdien, Hoytema Van Konijnenburg, David P., Van Der Wal, Maria M., Giovannone, Barbara, Mocholi, Enric, Vazirpanah, Nadia, Broen, Jasper C., Hijnen, Dirkjan, Oldenburg, Bas, Coffer, Paul J., Vastert, Sebastian J., Prakken, Berent J., Spierings, Eric, Pandit, Aridaman, Mokry, Michal, and Van Wijk, Femke

Published
2018

8. PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation

Author

Petrelli, Alessandra, Mijnheer, Gerdien, Hoytema Van Konijnenburg, David P., Van Der Wal, Maria M., Giovannone, Barbara, Mocholi, Enric, Vazirpanah, Nadia, Broen, Jasper C., Hijnen, Dirkjan, Oldenburg, Bas, Coffer, Paul J., Vastert, Sebastian J., Prakken, Berent J., Spierings, Eric, Pandit, Aridaman, Mokry, Michal, Van Wijk, Femke, Petrelli, Alessandra, Mijnheer, Gerdien, Hoytema Van Konijnenburg, David P., Van Der Wal, Maria M., Giovannone, Barbara, Mocholi, Enric, Vazirpanah, Nadia, Broen, Jasper C., Hijnen, Dirkjan, Oldenburg, Bas, Coffer, Paul J., Vastert, Sebastian J., Prakken, Berent J., Spierings, Eric, Pandit, Aridaman, Mokry, Michal, and Van Wijk, Femke

Published
2018

9. PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation

Author

Petrelli, Alessandra, Mijnheer, Gerdien, Hoytema Van Konijnenburg, David P., Van Der Wal, Maria M., Giovannone, Barbara, Mocholi, Enric, Vazirpanah, Nadia, Broen, Jasper C., Hijnen, Dirkjan, Oldenburg, Bas, Coffer, Paul J., Vastert, Sebastian J., Prakken, Berent J., Spierings, Eric, Pandit, Aridaman, Mokry, Michal, Van Wijk, Femke, Petrelli, Alessandra, Mijnheer, Gerdien, Hoytema Van Konijnenburg, David P., Van Der Wal, Maria M., Giovannone, Barbara, Mocholi, Enric, Vazirpanah, Nadia, Broen, Jasper C., Hijnen, Dirkjan, Oldenburg, Bas, Coffer, Paul J., Vastert, Sebastian J., Prakken, Berent J., Spierings, Eric, Pandit, Aridaman, Mokry, Michal, and Van Wijk, Femke

Published
2018

10. PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation

Author

MMB Research line 1, Infection & Immunity, Lab Dermatologie/Allergologie, Cancer, CMM Groep Coffer, Translationele immunologie, Unit Opleiding Reumat./Klin. Immunologie, MS MDL 1, Onderzoek, CMM Sectie Stem Cells, Regenerative Medicine and Stem Cells, Immuno/reuma onderzoek 5 (Vastert2), Child Health, Immuno/reuma patientenzorg, Circulatory Health, CDL Patiëntenzorg MI, MDL onderzoek 1, Immuno/reuma onderzoek 4, Petrelli, Alessandra, Mijnheer, Gerdien, Hoytema Van Konijnenburg, David P., Van Der Wal, Maria M., Giovannone, Barbara, Mocholi, Enric, Vazirpanah, Nadia, Broen, Jasper C., Hijnen, Dirkjan, Oldenburg, Bas, Coffer, Paul J., Vastert, Sebastian J., Prakken, Berent J., Spierings, Eric, Pandit, Aridaman, Mokry, Michal, Van Wijk, Femke, MMB Research line 1, Infection & Immunity, Lab Dermatologie/Allergologie, Cancer, CMM Groep Coffer, Translationele immunologie, Unit Opleiding Reumat./Klin. Immunologie, MS MDL 1, Onderzoek, CMM Sectie Stem Cells, Regenerative Medicine and Stem Cells, Immuno/reuma onderzoek 5 (Vastert2), Child Health, Immuno/reuma patientenzorg, Circulatory Health, CDL Patiëntenzorg MI, MDL onderzoek 1, Immuno/reuma onderzoek 4, Petrelli, Alessandra, Mijnheer, Gerdien, Hoytema Van Konijnenburg, David P., Van Der Wal, Maria M., Giovannone, Barbara, Mocholi, Enric, Vazirpanah, Nadia, Broen, Jasper C., Hijnen, Dirkjan, Oldenburg, Bas, Coffer, Paul J., Vastert, Sebastian J., Prakken, Berent J., Spierings, Eric, Pandit, Aridaman, Mokry, Michal, and Van Wijk, Femke

Published
2018

11. PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation

Author

Petrelli, Alessandra, Mijnheer, Gerdien, Hoytema Van Konijnenburg, David P., Van Der Wal, Maria M., Giovannone, Barbara, Mocholi, Enric, Vazirpanah, Nadia, Broen, Jasper C., Hijnen, Dirkjan, Oldenburg, Bas, Coffer, Paul J., Vastert, Sebastian J., Prakken, Berent J., Spierings, Eric, Pandit, Aridaman, Mokry, Michal, Van Wijk, Femke, Petrelli, Alessandra, Mijnheer, Gerdien, Hoytema Van Konijnenburg, David P., Van Der Wal, Maria M., Giovannone, Barbara, Mocholi, Enric, Vazirpanah, Nadia, Broen, Jasper C., Hijnen, Dirkjan, Oldenburg, Bas, Coffer, Paul J., Vastert, Sebastian J., Prakken, Berent J., Spierings, Eric, Pandit, Aridaman, Mokry, Michal, and Van Wijk, Femke

Abstract

Chronic inflammatory diseases are characterized by recurrent inflammatory attacks in the tissues mediated by autoreactive T cells. Identity and functional programming of CD8+ T cells at the target site of inflammation still remain elusive. One key question is whether, in these antigen-rich environments, chronic stimulation leads to CD8+ T cell exhaustion comparable to what is observed in infectious disease contexts. In the synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients, a model of chronic inflammation, an overrepresentation of PD-1+CD8+ T cells was found. Gene expression profiling, gene set enrichment analysis, functional studies, and extracellular flux analysis identified PD-1+CD8+ T cells as metabolically active effectors, with no sign of exhaustion. Furthermore, PD-1+CD8+ T cells were enriched for a tissue-resident memory (Trm) cell transcriptional profile and demonstrated increased clonal expansion compared with the PD-1- counterpart, suggesting antigen-driven expansion of locally adapted cells. Interestingly, this subset was also found increased in target tissues in other human chronic inflammatory diseases. These data indicate that local chronic inflammation drives the induction and expansion of CD8+ T cells endowed with potential detrimental properties. Together, these findings lay the basis for investigation of PD-1-expressing CD8+ T cell targeting strategies in human chronic inflammatory diseases.

Published
2018

12. Biomarkers in atopic dermatitis

Author

Bruijnzeel-Koomen, Carla, Hijnen, DirkJan, Nierkens, Stefan, Thijs, J.L., Bruijnzeel-Koomen, Carla, Hijnen, DirkJan, Nierkens, Stefan, and Thijs, J.L.

Published
2017

13. Biomarkers in atopic dermatitis

Author

Bruijnzeel-Koomen, Carla, Hijnen, DirkJan, Nierkens, Stefan, Thijs, J.L., Bruijnzeel-Koomen, Carla, Hijnen, DirkJan, Nierkens, Stefan, and Thijs, J.L.

Published
2017

14. Biomarkers in atopic dermatitis

Author

Unit Opleiding Dermatologie, Infection & Immunity, Bruijnzeel-Koomen, Carla, Hijnen, DirkJan, Nierkens, Stefan, Thijs, J.L., Unit Opleiding Dermatologie, Infection & Immunity, Bruijnzeel-Koomen, Carla, Hijnen, DirkJan, Nierkens, Stefan, and Thijs, J.L.

Published
2017

15. New Developments in Biomarkers for Atopic Dermatitis

Author

Thijs, Judith L, van Seggelen, Wouter, Bruijnzeel-Koomen, Carla, de Bruin-Weller, Marjolein, Hijnen, DirkJan, Thijs, Judith L, van Seggelen, Wouter, Bruijnzeel-Koomen, Carla, de Bruin-Weller, Marjolein, and Hijnen, DirkJan

Published
2015

16. Brief report: Enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid

Author

Leijten, Emmerik F A, van Kempen, Tessa S., Boes, Marianne, Michels-van Amelsfort, Jocea M R, Hijnen, Dirkjan, Hartgring, Sarita A Y, van Roon, Joel A G, Wenink, Mark H., Radstake, Timothy R D J, Leijten, Emmerik F A, van Kempen, Tessa S., Boes, Marianne, Michels-van Amelsfort, Jocea M R, Hijnen, Dirkjan, Hartgring, Sarita A Y, van Roon, Joel A G, Wenink, Mark H., and Radstake, Timothy R D J

Published
2015

17. TSLP is differentially regulated by vitamin D3 and cytokines in human skin

Author

Landheer, Janneke, Giovannone, Barbara, Sadekova, Svetlana, Tjabringa, Sandra, Hofstra, Claudia, Dechering, Koen, Bruijnzeel-Koomen, Carla, Chang, Charlie, Ying, Yu, de Waal Malefyt, Rene, Hijnen, DirkJan, Knol, Edward, Landheer, Janneke, Giovannone, Barbara, Sadekova, Svetlana, Tjabringa, Sandra, Hofstra, Claudia, Dechering, Koen, Bruijnzeel-Koomen, Carla, Chang, Charlie, Ying, Yu, de Waal Malefyt, Rene, Hijnen, DirkJan, and Knol, Edward

Published
2015

18. Biomarkers for atopic dermatitis : a systematic review and meta-analysis

Author

Thijs, Judith, Krastev, Todor, Weidinger, Stephan, Buckens, Constantinus F, de Bruin-Weller, Marjolein, Bruijnzeel-Koomen, Carla, Flohr, Carsten, Hijnen, DirkJan, Thijs, Judith, Krastev, Todor, Weidinger, Stephan, Buckens, Constantinus F, de Bruin-Weller, Marjolein, Bruijnzeel-Koomen, Carla, Flohr, Carsten, and Hijnen, DirkJan

Published
2015

19. New Developments in Biomarkers for Atopic Dermatitis

Author

Thijs, Judith L., Seggelen, Wouter van, Bruijnzeel-Koomen, Carla, Bruin-Weller, Marjolein de, Hijnen, DirkJan, Thijs, Judith L., Seggelen, Wouter van, Bruijnzeel-Koomen, Carla, Bruin-Weller, Marjolein de, and Hijnen, DirkJan

Published
2015

20. Brief report: Enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid

Author

Leijten, Emmerik F A, van Kempen, Tessa S., Boes, Marianne, Michels-van Amelsfort, Jocea M R, Hijnen, Dirkjan, Hartgring, Sarita A Y, van Roon, Joel A G, Wenink, Mark H., Radstake, Timothy R D J, Leijten, Emmerik F A, van Kempen, Tessa S., Boes, Marianne, Michels-van Amelsfort, Jocea M R, Hijnen, Dirkjan, Hartgring, Sarita A Y, van Roon, Joel A G, Wenink, Mark H., and Radstake, Timothy R D J

Published
2015

21. Biomarkers for atopic dermatitis : a systematic review and meta-analysis

Author

Thijs, Judith, Krastev, Todor, Weidinger, Stephan, Buckens, Constantinus F, de Bruin-Weller, Marjolein, Bruijnzeel-Koomen, Carla, Flohr, Carsten, Hijnen, DirkJan, Thijs, Judith, Krastev, Todor, Weidinger, Stephan, Buckens, Constantinus F, de Bruin-Weller, Marjolein, Bruijnzeel-Koomen, Carla, Flohr, Carsten, and Hijnen, DirkJan

Published
2015

22. TSLP is differentially regulated by vitamin D3 and cytokines in human skin

Author

Landheer, Janneke, Giovannone, Barbara, Sadekova, Svetlana, Tjabringa, Sandra, Hofstra, Claudia, Dechering, Koen, Bruijnzeel-Koomen, Carla, Chang, Charlie, Ying, Yu, de Waal Malefyt, Rene, Hijnen, DirkJan, Knol, Edward, Landheer, Janneke, Giovannone, Barbara, Sadekova, Svetlana, Tjabringa, Sandra, Hofstra, Claudia, Dechering, Koen, Bruijnzeel-Koomen, Carla, Chang, Charlie, Ying, Yu, de Waal Malefyt, Rene, Hijnen, DirkJan, and Knol, Edward

Published
2015

23. New Developments in Biomarkers for Atopic Dermatitis

Author

Thijs, Judith L., Seggelen, Wouter van, Bruijnzeel-Koomen, Carla, Bruin-Weller, Marjolein de, Hijnen, DirkJan, Thijs, Judith L., Seggelen, Wouter van, Bruijnzeel-Koomen, Carla, Bruin-Weller, Marjolein de, and Hijnen, DirkJan

Published
2015

24. New Developments in Biomarkers for Atopic Dermatitis

Author

Thijs, Judith L, van Seggelen, Wouter, Bruijnzeel-Koomen, Carla, de Bruin-Weller, Marjolein, Hijnen, DirkJan, Thijs, Judith L, van Seggelen, Wouter, Bruijnzeel-Koomen, Carla, de Bruin-Weller, Marjolein, and Hijnen, DirkJan

Published
2015

25. Biomarkers for atopic dermatitis : a systematic review and meta-analysis

Author

Thijs, Judith, Krastev, Todor, Weidinger, Stephan, Buckens, Constantinus F, de Bruin-Weller, Marjolein, Bruijnzeel-Koomen, Carla, Flohr, Carsten, Hijnen, DirkJan, Thijs, Judith, Krastev, Todor, Weidinger, Stephan, Buckens, Constantinus F, de Bruin-Weller, Marjolein, Bruijnzeel-Koomen, Carla, Flohr, Carsten, and Hijnen, DirkJan

Published
2015

26. New Developments in Biomarkers for Atopic Dermatitis

Author

Thijs, Judith L, van Seggelen, Wouter, Bruijnzeel-Koomen, Carla, de Bruin-Weller, Marjolein, Hijnen, DirkJan, Thijs, Judith L, van Seggelen, Wouter, Bruijnzeel-Koomen, Carla, de Bruin-Weller, Marjolein, and Hijnen, DirkJan

Published
2015

27. TSLP is differentially regulated by vitamin D3 and cytokines in human skin

Author

Landheer, Janneke, Giovannone, Barbara, Sadekova, Svetlana, Tjabringa, Sandra, Hofstra, Claudia, Dechering, Koen, Bruijnzeel-Koomen, Carla, Chang, Charlie, Ying, Yu, de Waal Malefyt, Rene, Hijnen, DirkJan, Knol, Edward, Landheer, Janneke, Giovannone, Barbara, Sadekova, Svetlana, Tjabringa, Sandra, Hofstra, Claudia, Dechering, Koen, Bruijnzeel-Koomen, Carla, Chang, Charlie, Ying, Yu, de Waal Malefyt, Rene, Hijnen, DirkJan, and Knol, Edward

Published
2015

28. New Developments in Biomarkers for Atopic Dermatitis

Author

Thijs, Judith L., Seggelen, Wouter van, Bruijnzeel-Koomen, Carla, Bruin-Weller, Marjolein de, Hijnen, DirkJan, Thijs, Judith L., Seggelen, Wouter van, Bruijnzeel-Koomen, Carla, Bruin-Weller, Marjolein de, and Hijnen, DirkJan

Published
2015

29. Brief report: Enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid

Author

Leijten, Emmerik F A, van Kempen, Tessa S., Boes, Marianne, Michels-van Amelsfort, Jocea M R, Hijnen, Dirkjan, Hartgring, Sarita A Y, van Roon, Joel A G, Wenink, Mark H., Radstake, Timothy R D J, Leijten, Emmerik F A, van Kempen, Tessa S., Boes, Marianne, Michels-van Amelsfort, Jocea M R, Hijnen, Dirkjan, Hartgring, Sarita A Y, van Roon, Joel A G, Wenink, Mark H., and Radstake, Timothy R D J

Published
2015

30. Brief report: Enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid

Author

Translationele immunologie, Infection & Immunity, Immuno/reuma onderzoek 2 (Boes), Child Health, CTI Boes, MS Reumatologie/Immunologie/Infectie, MS Dermatologie/Allergologie, Unit Opleiding Reumat./Klin. Immunologie, Leijten, Emmerik F A, van Kempen, Tessa S., Boes, Marianne, Michels-van Amelsfort, Jocea M R, Hijnen, Dirkjan, Hartgring, Sarita A Y, van Roon, Joel A G, Wenink, Mark H., Radstake, Timothy R D J, Translationele immunologie, Infection & Immunity, Immuno/reuma onderzoek 2 (Boes), Child Health, CTI Boes, MS Reumatologie/Immunologie/Infectie, MS Dermatologie/Allergologie, Unit Opleiding Reumat./Klin. Immunologie, Leijten, Emmerik F A, van Kempen, Tessa S., Boes, Marianne, Michels-van Amelsfort, Jocea M R, Hijnen, Dirkjan, Hartgring, Sarita A Y, van Roon, Joel A G, Wenink, Mark H., and Radstake, Timothy R D J

Published
2015

31. TSLP is differentially regulated by vitamin D3 and cytokines in human skin

Author

MS Dermatologie/Allergologie, Lab Dermatologie/Allergologie, Infection & Immunity, CTI, Landheer, Janneke, Giovannone, Barbara, Sadekova, Svetlana, Tjabringa, Sandra, Hofstra, Claudia, Dechering, Koen, Bruijnzeel-Koomen, Carla, Chang, Charlie, Ying, Yu, de Waal Malefyt, Rene, Hijnen, DirkJan, Knol, Edward, MS Dermatologie/Allergologie, Lab Dermatologie/Allergologie, Infection & Immunity, CTI, Landheer, Janneke, Giovannone, Barbara, Sadekova, Svetlana, Tjabringa, Sandra, Hofstra, Claudia, Dechering, Koen, Bruijnzeel-Koomen, Carla, Chang, Charlie, Ying, Yu, de Waal Malefyt, Rene, Hijnen, DirkJan, and Knol, Edward

Published
2015

32. Biomarkers for atopic dermatitis: a systematic review and meta-analysis

Author

Unit Opleiding Dermatologie, Infection & Immunity, MS Dermatologie/Allergologie, Thijs, Judith, Krastev, Todor, Weidinger, Stephan, Buckens, Constantinus F, de Bruin-Weller, Marjolein, Bruijnzeel-Koomen, Carla, Flohr, Carsten, Hijnen, DirkJan, Unit Opleiding Dermatologie, Infection & Immunity, MS Dermatologie/Allergologie, Thijs, Judith, Krastev, Todor, Weidinger, Stephan, Buckens, Constantinus F, de Bruin-Weller, Marjolein, Bruijnzeel-Koomen, Carla, Flohr, Carsten, and Hijnen, DirkJan

Published
2015

33. New Developments in Biomarkers for Atopic Dermatitis

Author

Infection & Immunity, MS Dermatologie/Allergologie, Unit Opleiding Dermatologie, Thijs, Judith L, van Seggelen, Wouter, Bruijnzeel-Koomen, Carla, de Bruin-Weller, Marjolein, Hijnen, DirkJan, Infection & Immunity, MS Dermatologie/Allergologie, Unit Opleiding Dermatologie, Thijs, Judith L, van Seggelen, Wouter, Bruijnzeel-Koomen, Carla, de Bruin-Weller, Marjolein, and Hijnen, DirkJan

Published
2015

34. New Developments in Biomarkers for Atopic Dermatitis

Author

Thijs, Judith L., Seggelen, Wouter van, Bruijnzeel-Koomen, Carla, Bruin-Weller, Marjolein de, Hijnen, DirkJan, Thijs, Judith L., Seggelen, Wouter van, Bruijnzeel-Koomen, Carla, Bruin-Weller, Marjolein de, and Hijnen, DirkJan

Published
2015

35. New developments in biomarkers for atopic dermatitis

Author

Thijs, Judith L., Van Seggelen, Wouter, Bruijnzeel-Koomen, Carla, De Bruin-Weller, Marjolein, Hijnen, Dirkjan, Thijs, Judith L., Van Seggelen, Wouter, Bruijnzeel-Koomen, Carla, De Bruin-Weller, Marjolein, and Hijnen, Dirkjan

Abstract

The application of biomarkers in medicine is evolving. Biomarkers do not only give us a better understanding of pathogenesis, but also increase treatment efficacy and safety, further enabling more precise clinical care. This paper focuses on the current use of biomarkers in atopic dermatitis, new developments and future perspectives. Biomarkers can be used for many different purposes, including the objective determination of disease severity, confirmation of clinical diagnosis, and to predict response to treatment. In atopic dermatitis, many biomarkers have been investigated as a marker for disease severity. Currently serum thymus and activation-regulated chemokine (TARC) is the superior biomarker for assessing disease severity. However, we have recently shown that the use of a panel of serum biomarkers is more suitable for assessing disease severity than an individual biomarker. In this overview, we will discuss alternative sources for biomarkers, such as saliva and capillary blood, which can increase the user friendliness of biomarkers in atopic dermatitis (AD). Both methods offer simple, non-invasive and cost effective alternatives to venous blood. This provides great translational and clinical potential. Biomarkers will play an increasingly important role in AD research and personalized medicine. The use of biomarkers will enhance the efficacy of AD treatment by facilitating the individualization of therapy targeting the patients’ specific biological signature and also by providing tools for predicting and monitoring of therapeutic response.

Published
2015

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