Changes in the anticitrullinated peptide antibody response in relation to therapeutic outcome in early rheumatoid arthritis: results from the SWEFOT trial

Abstract

ObjectiveTo determine the relationship between changes in antibody levels towards citrullinated peptides derived from different candidate autoantigens and therapeutic outcome in early rheumatoid arthritis (RA).MethodsBaseline and 3-month serum samples from 316 patients with early RA enrolled in the Swedish Farmacotherapy (SWEFOT) trial were analysed for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib) and α-enolase (CEP-1). At 3-month follow-up, methotrexate monotherapy-inadequate responders were randomised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab. In these patients, anticitrullinated peptide antibodies (ACPA) were also assessed at 12 and 24 months. The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression.ResultsDuring the 2-year follow-up, the proportion of patients testing positive declined significantly regarding antibodies to cVim, cFib and CEP-1, while anti-CCP antibody occurrence remained stable over time. Turning anti-cVim antibody negative was most common, and anti-cVim antibody seroreversion during the first three months associated with significantly less 2-year radiographic progression compared with patients who remained positive. Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy, with no significant relation to treatment regimen or radiographic progression.ConclusionsThe influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities, and early disappearance of anti-cVim antibodies associated with better radiological outcome. Thus, these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA.Trial registration numberWHO database at the Karolinska institute: CT20080004; and clinicaltrials.gov: NCT00764725.

Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis

“…Also, Cambridge et al showed that both ACPA IgG and IgA decreased after rituximab treatment [25]. TNF inhibition seems to associate with ACPA reductions in early RA [29], but not in established disease [24,29]. Thus, reduced SC expression could lead to lower levels of SIgA.…”

“…The expression of SC is dependent upon tumour necrosis factor (TNF) [27]-induced nuclear factor kappa B (NF-κB) activation [28]. TNF inhibition seems to associate with ACPA reductions in early RA [29], but not in established disease [24,29]. Hence, it would be relevant to study the impact of anti-TNF therapy regarding ACPA SIgA levels, but in the current study the statistical power was insufficient for investigation of any specific impact of bDMARDs on ACPA isotype response.…”

How well do ACPA discriminate and predict RA in the general population: a study based on 12 590 population-representative Swedish twins

“…These studies demonstrate that ACPA appear up to several years before disease onset and predict RA development. Further, diversification with recognition of an increasing number of citrullinated peptides and concomitant rise in ACPA titres occur before disease onset,5 10 11 to reach a fairly stable repertoire once the RA classification criteria are fulfilled 13 14. A few small studies have been performed on individuals without signs and/or symptoms of the disease but at an elevated risk of developing arthritis (eg, symptom-free first-degree relatives of patients with RA), indicating lower titres and fewer ACPA reactivities as compared with their RA probands, but higher concentrations compared with population controls 8 15–18…”

Diagnostic and prognostic potential of joint imaging in patients with anti-citrullinated protein antibodies

“…The posttranslational shapes can be seen as antigens generating immune responses which results in the production of ACPAs with ≥95% specificity for RA [1]. Several studies confirm that the presence of ACPAs associates with accelerated bone erosions in RA [11][12][13]. To detect ACPAs, several assays have been developed, for instance employing filaggrin-derived peptides (CCP-assay), mutated citrullinated vimentin (MCV-assay), and viral citrullinated peptides (VCPassay).…”