Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab

Abstract

Rheumatoid arthritis (RA) is characterized by the presence of circulating rheumatoid factor (RF) and anticitrullinated peptide
antibodies (ACPA), which are positive in about 70–80% of patients. APCA have a higher specificity and therefore a higher diagnostic
power than RF, but are less informative than RF in monitoring the course of the disease in patients under treatment. Recently,
it has been reported that the anticitrullinated vimentin (a-MCV) antibody test can identify a particular subgroup of APCA
that may be negative for anticyclic citrullinated peptide (a-CCP) antibodies. Concerning RF, the RF IgA isotype has been described
as a more specific marker of erosive joint damage than total RF. The aim of our study was to monitor the levels of a-CCP,
a-MCV, total RF and RF IgA in the follow-up of patients with RA treated with B-lymphocytedepletive rituximab (RTX), to detect
any differences or peculiarities in patterns of these autoantibodies, especially in relation to their potential use as predictive
markers of therapeutic response. We studied 30 patients with RA treated with RTX. All patients were previously unresponsive
to at least 6 months of therapy with disease-modifying antirheumatic drugs (DMARDs; methotrexate, leflunomide, cyclosporine,
chloroquine) and/or at least 6 months of therapy with anti-TNF biologics. The evaluation of response to RTX was made at month
+6 using the EULAR criteria (DAS28). a-CCP, a-MCV, total RF and RF IgA were determined at baseline (before the first infusion
of RTX) and after 1, 3 and 6 months. In serum samples obtained before treatment two cytokines essential for Blymphocyte proliferation,
interleukin 6 (IL-6) and B-lymphocyte stimulator (BLyS) were also determined. In all patients a significant and consistent
reduction in all the tested antibodies was found during follow-up, with no differences in respect of the degree of response
to RTX. Of note, at baseline, generally a higher titre of all autoantibodies was seen in patients who then showed a better
response to RTX. Finally, there were no differences in serum concentrations of IL-6 and BLyS in patients in relation to the
presence or absence of the autoantibodies investigated, nor was there any significant correlation between the serum concentrations
of the cytokines and the titres of the autoantibodies. Thus, neither a-MCV compared to a- CCP, nor RF IgA compared to routine
total RF, provided any additional predictive information in the follow-up of patients with RA treated with RTX.

KeywordsAnticitrullinated peptide antibodies-Antimodified citrullinated vimentin antibodies-Rheumatoid factor-Rheumatoid arthritis-Rituximab