In RA, becoming seronegative over the first year of treatment does not translate to better chances of drug-free remission

Moel, Emma C. de; Derksen, V.; Trouw, Leendert A.; Bang, Holger; Goekoop-Ruiterman, Yvonne P M; Steup-Beekman, Gerda M; Huizinga, Tom W J; Allaart, Cornelia F; Toes, René; Woude, Diane van der

doi:10.1136/annrheumdis-2018-213823

Cited by 14 publications

(14 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The slopes of the levels along follow-up are relevant to appreciate the immunological evolution, which was different for RF and ACPA. Several studies have shown that improvement in disease activity is accompanied by decrease in RF levels,27–31 although some other studies did not observe this 18 19 32. A unique feature of this study is that a prolonged period of absence of clinical synovitis is observed, which is a much more stringent outcome than improvement in disease activity scores.…”

Section: Discussionmentioning

confidence: 57%

“…The observations described indicate that both are infrequent and not associated with relevant outcomes such as radiographic damage, functional status or the disease activity score 15–18. In only one study, the association between seroreversion and drug-free remission was analysed and no association was observed 19. However, autoantibody levels were only determined at disease presentation and at 1 year of follow-up, thus generally years before achievement of drug-free remission.…”

Section: Introductionmentioning

confidence: 98%

“…However, autoantibody levels were only determined at disease presentation and at 1 year of follow-up, thus generally years before achievement of drug-free remission. In addition, follow-up of patients after the achievement of drug-free remission was limited 19…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Does immunological remission, defined as disappearance of autoantibodies, occur with current treatment strategies? A long-term follow-up study in rheumatoid arthritis patients who achieved sustained DMARD-free status

et al. 2019

View full text Add to dashboard Cite

ObjectivesSustained disease-modifying antirheumatic drug (DMARD)-free status, the sustained absence of synovitis after cessation of DMARD therapy, is infrequent in autoantibody-positive rheumatoid arthritis (RA), but approximates cure (ie, disappearance of signs and symptoms). It was recently suggested that immunological remission, defined as disappearance of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), underlies this outcome. Therefore, this long-term observational study determined if autoantibodies disappear in RA patients who achieved sustained DMARD-free remission.MethodsWe studied 95 ACPA-positive and/or RF-positive RA patients who achieved DMARD-free remission after median 4.8 years and kept this status for the remaining follow-up (median 4.2 years). Additionally, 21 autoantibody-positive RA patients with a late flare, defined as recurrence of clinical synovitis after a DMARD-free status of ≥1 year, and 45 autoantibody-positive RA patients who were unable to stop DMARD therapy (during median 10 years) were studied. Anti-cyclic citrullinated peptide 2 (anti-CCP2) IgG, IgM and RF IgM levels were measured in 587 samples obtained at diagnosis, before and after achieving DMARD-free remission.Results13% of anti-CCP2 IgG-positive RA patients had seroreverted when achieving remission. In RA patients with a flare and persistent disease this was 8% and 6%, respectively (p=0.63). For anti-CCP2 IgM and RF IgM, similar results were observed. Evaluating the estimated slope of serially measured levels revealed that RF levels decreased more in patients with than without remission (p<0.001); the course of anti-CCP2 levels was not different (p=0.66).ConclusionsSustained DMARD-free status in autoantibody-positive RA was not paralleled by an increased frequency of reversion to autoantibody negativity. This form of immunological remission may therefore not be a treatment target in patients with classified RA.

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Does immunological remission, defined as disappearance of autoantibodies, occur with current treatment strategies? A long-term follow-up study in rheumatoid arthritis patients who achieved sustained DMARD-free status

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Over the last decade, therapies targeting B cells—such as the anti‐CD20 therapeutic antibody rituximab—have proven effective in RA, indicating a potential role for (autoreactive) B cells in disease pathogenesis . Intriguingly, clinical efficacy does not seem to be closely linked with detectable changes in AMPA profiles, and even at low disease activity, patients often remain autoantibody‐positive . Although it remains possible that anti‐CD20 treatment induces yet unidentified changes in the autoantibody response, these findings suggest that autoantibodies themselves may have a limited role in driving the disease.…”

Section: From Antibodies To B Cellsmentioning

confidence: 99%

“…92 Intriguingly, clinical efficacy does not seem to be closely linked with detectable changes in AMPA profiles, and even at low disease activity, patients often remain autoantibody-positive. 6,93,94 Although it remains possible that anti-CD20 treatment induces yet unidentified changes in the autoantibody response, these findings suggest that autoantibodies themselves may have a limited role in driving the disease. Whereas the clinical efficacy of CD20-depletion points toward a role for B cells in RA pathogenesis, the role of plasma cells in RA remains to be elucidated.…”

Section: Importantly It Is Unclear What Role Citrulline-reactive B Cmentioning

confidence: 99%

Autoantibodies and B Cells: The ABC of rheumatoid arthritis pathophysiology

Volkov

Schie

Woude

2019

Immunological Reviews

119

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. In the last few decades, new insights into RA‐specific autoantibodies and B cells have greatly expanded our understanding of the disease. The best‐known autoantibodies in RA—rheumatoid factor (RF) and anti‐citrullinated protein antibodies (ACPA)—are present long before disease onset, and both responses show signs of maturation around the time of the first manifestation of arthritis. A very intriguing characteristic of ACPA is their remarkably high abundance of variable domain glycans. Since these glycans may convey an important selection advantage of citrulline‐reactive B cells, they may be the key to understanding the evolution of the autoimmune response. Recently discovered autoantibodies targeting other posttranslational modifications, such as anti‐carbamylated and anti‐acetylated protein antibodies, appear to be closely related to ACPA, which makes it possible to unite them under the term of anti‐modified protein antibodies (AMPA). Despite the many insights gained about these autoantibodies, it is unclear whether they are pathogenic or play a causal role in disease development. Autoreactive B cells from which the autoantibodies originate have also received attention as perhaps more likely disease culprits. The development of autoreactive B cells in RA largely depends on the interaction with T cells in which HLA “shared epitope” and HLA DERAA may play an important role. Recent technological advances made it possible to identify and characterize citrulline‐reactive B cells and acquire ACPA monoclonal antibodies, which are providing valuable insights and help to understand the nature of the autoimmune response underlying RA. In this review, we summarize what is currently known about the role of autoantibodies and autoreactive B cells in RA and we discuss the most prominent hypotheses aiming to explain the origins and the evolution of autoimmunity in RA.

show abstract

Age-associated B cells in autoimmune diseases

Mouat

Goldberg

Horwitz

2022

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Age-associated B cells (ABCs) are a transcriptionally and functionally unique B cell population. In addition to arising with age and following infection, ABCs are expanded during autoimmune disease, including those with systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. The exact nature of how ABCs impact disease remains unclear. Here, we review what is known regarding ABC development and distribution during diseases including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. We discuss possible mechanisms by which ABCs could contribute to disease, including the production of cytokines and autoantibodies or stimulation of T cells. Finally, we speculate on how ABCs might act as mediators between sex, infection, and autoimmune disease, and discuss avenues for further research.

show abstract

In RA, becoming seronegative over the first year of treatment does not translate to better chances of drug-free remission

Cited by 14 publications

References 6 publications

Does immunological remission, defined as disappearance of autoantibodies, occur with current treatment strategies? A long-term follow-up study in rheumatoid arthritis patients who achieved sustained DMARD-free status

Does immunological remission, defined as disappearance of autoantibodies, occur with current treatment strategies? A long-term follow-up study in rheumatoid arthritis patients who achieved sustained DMARD-free status

Autoantibodies and B Cells: The ABC of rheumatoid arthritis pathophysiology

Age-associated B cells in autoimmune diseases

Contact Info

Product

Resources

About