Article
Rheumatology
Eleftheria Pertsinidou, Saedis Saevarsdottir, Vivek Anand Manivel, Lars Klareskog, Lars Alfredsson, Linda Mathsson-Alm, Monika Hansson, Martin Cornillet, Guy Serre, Rikard Holmdahl, Karl Skriner, Per-Johan Jakobsson, Helga Westerlind, Johan Askling, Johan Roennelid
Summary: In early RA patients, ACPA is associated with a lower number of affected joints, while RF is associated with elevated systemic inflammation markers in an ACPA-dependent manner. This finding supports the in vitro models of ACPA and RF in immune complex-induced inflammation. These phenotypic associations are independent of classification criteria.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Dylan T. Bergstedt, Wyatt J. Tarter, Ryan A. Peterson, Marie L. Feser, Mark C. Parish, Christopher C. Striebich, M. Kristen Demoruelle, LauraKay Moss, Elizabeth A. Bemis, Jill M. Norris, V. Michael Holers, Jess D. Edison, Geoffrey M. Thiele, Ted R. Mikuls, Kevin D. Deane
Summary: In rheumatoid arthritis (RA), ACPA and RF are predictive markers for future RA. This study found that changes in RF isotypes were associated with an increased risk for developing RA, and SE was associated with an increased risk of RA. These findings are important for counseling individuals at-risk for RA and designing clinical trials for RA prevention.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Yibo He, Changrong Ge, Alex Moreno-Giro, Bingze Xu, Christian M. Beusch, Katalin Sandor, Jie Su, Lei Cheng, Erik Lonnblom, Christina Lundqvist, Linda M. Slot, Dongmei Tong, Vilma Urbonaviciute, Bibo Liang, Taotao Li, Gonzalo Fernandez Lahore, Mike Aoun, Vivianne Malmstrom, Theo Rispens, Patrik Ernfors, Camilla I. Svensson, Hans Ulrich Scherer, Rene E. M. Toes, Inger Gjertsson, Olov Ekwall, Roman A. Zubarev, Rikard Holmdahl
Summary: Although anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA), their in vivo functions remain unclear. In this study, monoclonal ACPAs derived from RA patients were expressed in mice and their functions were analyzed. One of the antibodies, clone E4, showed a protective effect against antibody-induced arthritis in mice, suggesting therapeutic potential for ACPAs in RA.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Chao-Yi Wu, Huang-Yu Yang, Shue-Fen Luo, Jenn-Haung Lai
Summary: RA is a chronic inflammatory disease involving synovial inflammation and articular destruction. RFs, ACPAs, and anti-CarP Abs have been identified as important autoantibodies in predicting and diagnosing RA, with potential implications for treatment response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Aase Hensvold, Lars Klareskog
Summary: Recent progress in understanding the etiology and molecular pathogenesis of rheumatoid arthritis (RA) has opened up new opportunities for personalized and targeted prevention strategies, aiming to prevent the disease before onset and understand the molecular pathogenesis of its different variants.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Rheumatology
Ketian Li, Wenxiu Mo, Lijun Wu, Xunyao Wu, Cainan Luo, Xinyue Xiao, Xinmiao Jia, Huaxia Yang, Yunyun Fei, Hua Chen, Fengchun Zhang, Yongzhe Li, Lidan Zhao, Xuan Zhang
Summary: This study identified nine novel autoantibodies in ACPA-negative RA, with anti-PTX3 and anti-DUSP11 showing the highest sensitivity. The combination of these two autoantibodies significantly increased the diagnostic sensitivity in ACPA-negative RA. The novel biomarkers provide potential diagnostic value for ACPA-negative RA patients.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Rheumatology
Nilasha Ghosh, Pankti Reid, Carlos Andres Aude, Jessica Kirschman, Susan Goodman, Vivian P. Bykerk, Amit Lakhanpal, Diviya Rajesh, Karmela K. Chan, William H. Robinson, Anne R. Bass
Summary: In this study, the expansion of ACPA epitopes in CCP+ICI-IA was compared with patients with RA. It was found that patients with ICI-IA had lower ACPA titres and targeted fewer ACPA epitopes compared to longstanding RA patients, and there were no significant differences in the presence of the shared epitope between ICI-IA patients and ICI controls. This suggests that ICI-IA may represent an accelerated model of RA pathogenesis.
Article
Immunology
Daniela Sieghart, Christian Konrad, Sascha Swiniarski, Helmuth Haslacher, Daniel Aletaha, Guenter Steiner
Summary: This study aimed to investigate the diagnostic performance of anti-CCP2 and anti-CCP3 IgG and IgA assays in patients with early RA, with a focus on the prognostic value of IgA ACPA. The results showed that the anti-CCP2 IgG and IgA assays had high specificity but low sensitivity. The anti-CCP3.1 assay had slightly higher sensitivity but lower specificity compared to the anti-CCP2 IgG assay.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Rheumatology
Lieve Van Hoovels, Bert Vander Cruyssen, Daniela Sieghart, Carolien Bonroy, Eszter Nagy, Rille Pullerits, Sasa Cucnik, Charlotte Dahle, Ingmar Heijnen, Luca Bernasconi, Farid Benkhadra, Laura Bogaert, Stefanie Van den Bremt, Ann Van Liedekerke, Geert Vanheule, Johan Robbrecht, Lucy Studholme, Claudine Wirth, Ruediger Mueller, Diego Kyburz, Christopher Sjowall, Alf Kastbom, Rok Jese, Boja Jovancevic, Emese Kiss, Peggy Jacques, Daniel Aletaha, Guenter Steiner, Patrick Verschueren, Xavier Bossuyt
Summary: This study aimed to refine the interpretation of RF and ACPA across commercial assays. By determining thresholds for antibody levels and assigning test result interval-specific LRs, clinical interpretation can be aligned for all RF and ACPA assays.
Review
Rheumatology
Anca Catrina, Akilan Krishnamurthy, Bence Rethi
Summary: ACPA may play a crucial role in the pathogenesis of RA, affecting the genetic and environmental risks in patients, leading to joint pain and bone loss. Research has shown that ACPAs can impact various cells, potentially triggering pathogenic pathways through multiple mechanisms.
Article
Rheumatology
Michelle D. van den Beukel, Tineke J. van Wesemael, Anna Titia W. Hoogslag, Nicole Borggreven, Tom W. J. Huizinga, Annette H. M. van der Helm-van Mil, Rene E. M. Toes, Diane van der Woude, Leendert A. Trouw
Summary: It has been found that the presence of anti-malondialdehyde-acetaldehyde adducts and anti-advanced glycation end-products autoantibodies is common in rheumatoid arthritis patients. These autoantibodies are associated with HLA genes, inflammation, and clinical outcomes.
Article
Immunology
Serena Bugatti, Laura Bogliolo, Antonio Manzo, Ludovico De Stefano, Paolo Delvino, Francesca Motta, Carlomaurizio Montecucco
Summary: ACPA positivity in early RA patients is associated with ongoing bone mineral density loss at the spine despite treatment, highlighting the need for strict monitoring for osteoporosis development.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Rheumatology
Nathalie Luurssen-Masurel, Elise van Mulligen, Angelique Elisabeth Adriana Maria Weel-Koenders, Johanna Maria Wilhelmina Hazes, Pascal Hendrik Pieter de Jong
Summary: This study compared the long-term clinical outcomes of three clinical arthritis phenotypes: undifferentiated arthritis (UA), autoantibody-negative (RA-) and autoantibody-positive RA (RA+). The results showed that there were differences in remission rates and sustained remission rates between these phenotypes. The data confirm that rheumatoid arthritis can be subdivided based on clinical phenotypes and that treatment should be stratified accordingly.
Article
Rheumatology
Fenne Wouters, Marc P. Maurits, Laurette van Boheemen, Marloes Verstappen, Kulveer Mankia, Xanthe M. E. Matthijssen, Annemarie L. Dorjee, Paul Emery, Rachel Knevel, Dirkjan van Schaardenburg, Rene E. M. Toes, Annette H. M. van der Helm-van Mil
Summary: HLA-SE and smoking act at different stages in the development of rheumatoid arthritis: smoking increases the risk of autoantibody and symptom development, while HLA-SE mediates symptom and inflammatory arthritis development. These findings enhance our understanding of the timing of key risk factors in RA development.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Immunology
Minjie Xu, Rong Du, Wenping Xing, Xueting Chen, Jian Wan, Shengqing Wang, Li Xiong, Kutty Selva Nandakumar, Rikard Holmdahl, Hui Geng
Summary: Citrullinated neoepitopes have been identified as key triggers for the synthesis of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. This study investigated the expression of citrullinated proteins and enzymes in human platelets and platelet-derived microparticles (PDP). The results revealed the presence of citrullinated autoantigens in platelets and PDPs, suggesting that they could be potential targets for ACPA in RA. These findings provide valuable insights into the role of platelets in triggering ACPA production in RA.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Rheumatology
Sophie I. E. Liem, Eva M. Hoekstra, Femke Bonte-Mineur, Cesar Magro Checa, Anne Schouffoer, Cornelia F. Allaart, Tom W. J. Huizinga, Sytske Anne Bergstra, Jeska K. de Vries-Bouwstra
Summary: This study evaluated the clinical efficiency of silver fibre gloves in reducing the burden of Raynaud's Phenomenon (RP) in SSc patients. The results showed that wearing silver fibre gloves had a similar effect on reducing RP burden compared to normal gloves. However, wearing silver fibre gloves may slightly increase the SHAQ score, which is clinically irrelevant. On the other hand, the occurrence of new digital ulcers was lower in patients wearing silver fibre gloves compared to those wearing normal gloves.
Article
Rheumatology
Luuk Wieske, Eileen W. Stalman, P. J. Koos van Dam, Laura Y. Kummer, Maurice Steenhuis, Zoe L. E. van Kempen, Joep Killestein, Adriaan G. Volkers, Sander W. Tas, Laura Boekel, Gertjan Wolbink, Anneke van der Kooi, Joost Raaphorst, Mark Lowenberg, Bart Takkenberg, Geert R. A. M. D'Haens, Phyllis Spuls, Marcel W. Bekkenk, Annelie H. Musters, Nicoline F. Post, Angela L. Bosma, Marc L. Hilhorst, Yosta Vegting, Frederique J. Bemelman, Alexandre Voskuyl, Bo Broens, Agner Parra Sanchez, Cecile A. C. M. van Els, Jelle De Wit, Abraham Rutgers, Karina de Leeuw, Barbara Horvath, Jan J. G. M. Verschuuren, Annabel M. Ruiter, Lotte van Ouwerkerk, Diane van der Woude, Cornelia F. Allaart, Y. K. Onno Teng, Pieter van Paassen, Matthias H. Busch, Papay B. P. Jallah, Esther Brusse, Pieter A. van Doorn, Adaja Elisabeth Baars, Dirkjan Hijnen, Corine R. G. Schreurs, W. Ludo Van der Pol, H. Stephan Goedee, Sofie Keijzer, Jim Keijser, Olvi Cristianawati, Anja ten Brinke, Niels J. M. Verstegen, Koos A. H. Zwinderman, S. Marieke van Ham, Taco W. Kuijpers, Theo Rispens, Filip Eftimov
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Allergy
Jana Koers, Rocco Sciarrillo, Ninotska I. L. Derksen, Esther M. Vletter, Yvonne E. Fillie-Grijpma, Elisabeth Raveling-Eelsing, Nuno A. G. Graca, Thiemo Leijser, Hendri H. Pas, L. Laura van Nijen-Vos, Maaike V. J. Braham, Anne-Marie Buisman, Jan de Jong, Angela I. Schriek, Anne P. Tio-Gillen, Y. K. Onno Teng, Maurice Steenhuis, Francis H. Swaneveld, Steven W. de Taeye, Marit J. van Gils, Jan J. G. M. Verschuuren, Bram Rutgers, Peter Heeringa, Barbara Horvath, Bart C. Jacobs, Karina de Leeuw, Casper F. M. Franssen, Agnes Veyradier, Paul Coppo, Kyra A. Gelderman, D. h S. Marieke van Ham, Cecile A. C. M. van Els, Diane van der Woude, Ruth Huizinga, Maartje G. Huijbers, Taco W. Kuijpers, Rene E. M. Toes, Nicolaas A. Bos, Theo Rispens
Summary: This study investigated the levels of Fab glycosylation on autoantibodies associated with various B cell-mediated autoimmune diseases and found that elevated Fab glycosylation is present in chronic autoimmune diseases. The increased Fab glycosylation was not limited to a specific subclass of IgG and was not caused by chronic antigen-stimulation. These findings suggest that disease-specific autoantibodies in chronic autoimmune diseases are enriched with Fab glycans.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Koos P. J. van Dam, Luuk Wieske, Eileen W. Stalman, Laura Y. L. Kummer, Jesse Roosen, Zoe L. E. van Kempen, Joep Killestein, Adriaan G. Volkers, Laura Boekel, Gerrit J. Wolbink, Anneke J. van der Kooi, Joost Raaphorst, Mark Lowenberg, R. Bart Takkenberg, Geert R. A. M. D'Haens, Phyllis I. Spuls, Marcel W. Bekkenk, Annelie H. Musters, Nicoline F. Post, Angela L. Bosma, Marc L. Hilhorst, Yosta Vegting, Frederike J. Bemelman, Alexandre E. Voskuyl, Bo Broens, Agner Parra Sanchez, Cecile A. C. M. van Els, Jelle de Wit, Abraham Rutgers, Karina de Leeuw, Barbara Horvath, Jan J. G. M. Verschuuren, Annabel M. Ruiter, Lotte van Ouwerkerk, Diane van der Woude, Renee C. F. Allaart, Y. K. Onno Teng, Pieter van Paassen, Matthias H. Busch, Papay B. P. Jallah, Esther Brusse, Pieter A. van Doorn, Adaja E. Baars, Dirk Jan Hijnen, Corine R. G. Schreurs, W. Ludo van der Pol, H. Stephan Goedee, Maurice Steenhuis, Sofie Keijzer, Jim B. D. Keijser, Olvi Cristianawati, Theo Rispens, Anja ten Brinke, Niels J. M. Verstegen, S. Marieke van Ham, Sander W. Tas, Taco W. Kuijpers, Filip Eftimov
Summary: This study aimed to assess changes in disease activity after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) and identify risk factors for increased disease activity. The results showed that a minority of patients reported increased disease activity after vaccination, but most cases were mild. Disease-related factors were found to have a major impact on the increased disease activity, rather than the vaccinations themselves.
JOURNAL OF AUTOIMMUNITY
(2023)
Review
Rheumatology
Theresa Kissel, Rene E. M. Toes, Thomas W. J. Huizinga, Manfred Wuhrer
Summary: Glycosylation is a common modification that affects protein stability and interactions. It plays a significant role in rheumatic diseases, influencing inflammatory processes and disease progression. Understanding the impact of glycosylation on plasma proteins, cells, and tissues opens up potential interventions for the treatment of these diseases.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Rheumatology
Sophie I. E. Liem, Sam Neppelenbroek, Cynthia M. Fehres, Corrie Wortel, Rene E. M. Toes, Tom W. J. Huizinga, Hans U. Scherer, Jeska K. de Vries-Bouwstra
Summary: A hallmark of disease pathogenesis of systemic sclerosis (SSc) is the presence of autoreactive B cell responses targeting nuclear proteins. Autoantibodies serve as diagnostic biomarkers in SSc and can help identify clinical phenotypes of the disease. Understanding the contribution of antinuclear autoantibodies and their underlying B cell response is crucial in the management and treatment of SSc.
SEMINARS IN ARTHRITIS AND RHEUMATISM
(2023)
Article
Veterinary Sciences
Sanne Kroos, Mahmoud Halima, Jan Kroon, Diane van der Woude, Onno C. Meijer, Maarten D. van de Wal, Peternella S. Verhave, Marcel J. M. Schaaf, Rene E. M. Toes, Arieke S. B. Kampstra
Summary: This study examined the effects of tramadol and paracetamol on the collagen antibody-induced arthritis model and found that they interfered with the therapeutic effects of glucocorticoids. Therefore, they are not suitable for evaluating the effects of glucocorticoids in this model.
LABORATORY ANIMALS
(2023)
Article
Rheumatology
Sascha L. Heckert, Petra C. E. Hissink-Muller, J. Merlijn van den Berg, Dieneke Schonenberg-Meinema, Lisette W. A. van Suijlekom-Smit, Marion A. J. van Rossum, Yvonne Koopman, Rebecca ten Cate, Danielle M. C. Brinkman, Tom W. J. Huizinga, Cornelia F. Allaart, Sytske Anne Bergstra
Summary: We studied the patterns of joint inflammation in JIA and found that joints with inflammation at disease onset tend to have recurrent episodes of inflammation during follow-up. This suggests that local factors may contribute to the occurrence of JIA flares.
Article
Rheumatology
Joy Ardjuna van der Pol, Guelsah Akdemir, Marianne van den Broek, Linda Dirven, Pit J. S. M. Kerstens, Willem F. Lems, Iris M. Markusse, Tom W. J. Huizinga, Cornelia F. Allaart
Summary: This study aimed to investigate whether repair of erosions and joint space narrowing (JSN) in rheumatoid arthritis (RA) occurs and whether clinical variables predict this. The eight-year follow-up data of the Best-study were analyzed, and patients with recent onset RA were randomly assigned to four treatment strategies. The results showed that repair of JSN and erosions was observed in 5.3% of the patients, but no significant associations were found with disease activity suppression or other predictors.
Article
Immunology
Miles D. Holborough-Kerkvliet, Sanne Kroos, Renee van de Wetering, Rene E. M. Toes
Summary: Autoimmune diseases are characterized by a breakdown of immunological tolerance to self, resulting in an abnormal immune response to self-antigens. The pathogenesis is driven by a complex interaction between autoreactive B and T cells. B cell targeting therapies, such as Rituximab, have shown efficacy in reducing symptoms of autoimmune diseases, but can also lead to infections. Therefore, antigen-specific approaches to target autoreactive cells are being investigated.
IMMUNOLOGY LETTERS
(2023)
Article
Medicine, Research & Experimental
Sanne Reijm, Joanneke C. Kwekkeboom, Nienke J. Blomberg, Jolien Suurmond, Diane van der Woude, Rene E. M. Toes, Hans U. Scherer
Summary: This study visualizes the B cell response against posttranslational modification antigens in autoimmune diseases. The results demonstrate extensive cross-reactivity of B cells against different antigens and the presence of PTM-directed plasmablasts in patients. The expression of CXCR3 suggests the potential involvement of chemokines in this process.
Article
Rheumatology
Corrie M. Wortel, Sophie I. E. Liem, Nina M. van Leeuwen, Maaike Boonstra, Cynthia M. Fehres, Lauran Stoeger, Tom W. J. Huizinga, Rene E. M. Toes, Jeska De Vries-Bouwstra, Hans U. Scherer
Summary: This study investigates the autoreactive B cell responses in ATA-positive and ACA-positive SSc patients. The results show that ATA-positive patients exhibit a more active B cell response, which is associated with the presence and severity of ILD. This may explain the differential responsiveness to B cell depleting therapy.
Article
Rheumatology
Emma C. de Moel, Leendert A. Trouw, Chikashi Terao, Nimmisha Govind, Mohammed Tikly, Hani El-Gabalawy, Irene Smolik, Holger Bang, Tom W. J. Huizinga, Rene E. M. Toes, Diane van der Woude
Summary: Rheumatoid arthritis (RA) occurs in different ethnic populations worldwide. This study revealed that anti-modified protein antibodies (AMPA) can be detected in RA patients across different continents and ethnicities, suggesting a common pathway involved in AMPA development. However, differences in AMPA levels and associated factors were observed among the different populations.
ARTHRITIS RESEARCH & THERAPY
(2023)
Article
Rheumatology
Sascha Louise Heckert, Johanna Maria Maassen, S. le Cessie, Y. P. M. Goekoop-Ruiterman, Melek Guler-Yuksel, Willem Lems, Tom W. J. Huizinga, Sytske Anne Bergstra, Cornelia F. Allaart
Summary: Excess mortality occurred in patients with RA after long-term treatment-to-target, with smoking as an important risk factor.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
