Restrictive IgG antibody response against mutated citrullinated vimentin predicts response to rituximab in patients with rheumatoid arthritis

Abstract

IntroductionAntibodies against mutated citrullinated vimentin (AMCV) represent a useful diagnostic marker with correlation to disease activity in patients with rheumatoid arthritis (RA). Since seropositivity for citrullinated autoantibodies was predictive for response to B-cell depleting therapy (BCDT) with rituximab (RTX), we investigated whether differences in antibody fine reactivity and immunoglobulin (Ig) isotype kinetics among AMCV-positive patients could provide additional information about outcome.MethodsA total of 50 AMCV IgG-positive RA patients (RTX responders (RRs) n = 37 and non-responders (NRRs) n = 13) were analyzed for reactivity against MCV epitopes and co-existent AMCV isotypes IgM and IgA. Antibody titers were determined by enzyme-linked immunosorbent assay at baseline and 24 weeks after the first cycle of RTX, and compared to kinetics of rheumatoid factor (RF) and antibodies against cyclic citrullinated peptide (ACCP).ResultsRecognized MCV epitopes by AMCV IgG of RRs and NRRs showed similar baseline patterns, with reducing reactivity in RRs and unchanged or even expanding reactivity in NRRs upon RTX treatment. At baseline, RRs were more frequently negative for AMCV subtypes, especially for IgA (68 %), compared to NRRs (31 %). Being AMCV IgA-negative at baseline indicated a good treatment response to RTX (negative predictive value = 0.86). Co-existence of AMCV IgA and IgG with stable titers upon treatment were associated with poorer responses to RTX. Furthermore, reductions of AMCV IgA levels upon RTX correlated with the improvement of 28-joint Disease Activity Score (DAS28). In comparison, subtypes of RF and ACCP were not of additional value for prediction of RTX response.ConclusionsRestrictive IgG seropositivity against MCV with treatment-associated decline in fine reactivity and titers was predictive for response to RTX. Double-positivity for AMCV IgG and IgA was associated with failure to respond to BCDT, suggesting a pathogenetic and less sensitive IgA-producing B-cell subset in NRRs.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0717-z) contains supplementary material, which is available to authorized users.

Anti-topoisomerase 1 antibody level changes after B сell depletion therapy in systemic sclerosis

“…Это в определенной степени соответствует данным, касающимся эффектов РТМ при других ИВРЗ. Так, при системной красной волчанке лечение РТМ приводит к снижению титров антител к двуспиральной ДНК, антител к кардиолипину [39][40][41] и антител к C1q [42], а у пациентов с ревматоидным артритом (РА) -ревматоидных факторов (РФ), антител к виментину и, в меньшей степени, антител к циклическим цитруллинированным белкам (АЦЦБ) [43][44][45]. Сходные результаты в отношении динамики антинейтрофильных цитоплазматических антител продемонстрированы у пациентов с системными васкулитами [46,47], антител к базальной мембране клубочка -у пациентов с синдромеом Гудпасчера [48,49], антител к рецептору фосфолипазы А2 -у пациентов с мембранозной нефропатией [50,51], антител к тромбоцитам -у пациентов с иммунной тромбоцитопенией [52], антител к эритроцитам -у пациентов с аутоиммунной гемолитической анемией [53], антител к островковым клеткам поджелудочной железы -у пациентов с сахарным диабетом [54].…”

Assessment of the association of baseline anti-CarbV and anti-MCV antibodies with response to treatment and radiographic progression in an RA population treated with either methotrexate or baricitinib: post-hoc analyses from RA-BEGIN

“…High titers of anti-CarbV IgM were associated with a poor response to MTX monotherapy, whereas a nonsignificant trend toward a better response with baricitinib and baricitinib plus MTX was observed. Other studies have shown that seropositive patients with RA have a better response to treatment modalities than seronegative patients [33] and that autoantibodies of the IgA subclass are predictive of a response to rituximab treatment [34]. However, patients with poor prognostic factors may still show a good response to treatment, as demonstrated in studies of patients positive for ACPA who responded to treatment with rituximab or abatacept [33,35].…”

Contribution of Multiplex Immunoassays to Rheumatoid Arthritis Management: From Biomarker Discovery to Personalized Medicine

“…An association between anti-MCV levels and extra-articular manifestations of RA has been detected [ 48 ]. Moreover, anti-MCV seems to also be a predictive marker of the response to rituximab treatment [ 49 ]. Several antibody types have been identified only in certain subsets of RA and present a complex pattern with partial overlaps between the different antibodies.…”