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.
ABSTRACT
BACKGROUND: In this study, we evaluated the analytical reliability and clinical sensitivity of two tests (indirect immunofluorescence and ELISA) for anti-DNA antibodies which use cell membrane DNA (cmDNA) as antigen (Wil2 NS lymphoblastoid B cell line). METHODS: We tested 97 sera of patients with systemic lupus erythematosus (SLE) and 140 control sera from healthy subjects or from patients with other systemic autoimmune diseases or infectious diseases. The results obtained with the two anti-cmDNA kits were compared with those obtained with three other methods: indirect immunofluorescence on Crithidia luciliae, ELISA anti-double-stranded DNA (anti-dsDNA) and ELISA anti-nucleosome. RESULTS: The diagnostic sensitivity was 85% for immunofluorescence cmDNA and 90% for ELISA cmDNA, i.e., much higher than that of Crithidia (51%) and ELISA dsDNA (71%) methods, and the same as that of the ELISA nucleosome test (85%). The specificity of the cmDNA tests proved lower (92% for immunofluorescence and 87% for ELISA) than that found by anti-dsDNA Crithidia (99%), ELISA (99%) and anti-nucleosome tests (100%). CONCLUSIONS: The results of our study indicate that cmDNA tests may be used as screening tests in patients with suspected SLE. The anti-nucleosome test offers the best diagnostic accuracy overall and can play an important role in the serological diagnosis of SLE.
