Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy

Abstract

Objective. To investigate the effect of infliximab treatment on antinuclear antibodies (ANAs), antidouble-stranded DNA (anti-dsDNA), antinucleosome, antihistone, and anti-extractable nuclear antigen (anti-ENA) antibodies in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients.Methods. Sera from 62 RA and 35 SpA patients treated with infliximab were tested at baseline and week 30 (RA group) or week 34 (SpA group). ANAs were tested by indirect immunofluorescence (IIF) on HEp-2 cells. Anti-dsDNA antibodies were detected by IIF on Crithidia luciliae and by enzyme-linked immunosorbent assay (ELISA) and were further isotyped with ␥, , and ␣ chain-specific conjugates at various time points. Antinucleosome antibodies were tested by ELISA. Antihistone and anti-ENA antibodies were detected by line immunoassay.Results. Initially, 32 of 62 RA patients and 6 of 35 SpA patients tested positive for ANAs. After infliximab treatment, these numbers shifted to 51 of 62 (P < 0.001) and 31 of 35 (P < 0.001), respectively. At baseline, none of the RA or SpA patients had anti-dsDNA antibodies. After infliximab treatment, 7 RA patients (P ‫؍‬ 0.016) and 6 SpA patients (P ‫؍‬ 0.031) became positive for anti-dsDNA antibodies. All 7 anti-dsDNA-positive RA patients had IgM and IgA anti-dsDNA antibodies.

Correlation between elevation of serum antinuclear antibody titer and decreased therapeutic efficacy in the treatment of Behçet’s disease with infliximab

“…Only one patient (5.9%) converted to anti-dsDNA antibody 6 positive during the follow-up period. These findings are consistent with previous studies of other autoimmune rheumatoid diseases, which reported that 25-71% and 4-46% patients became positive for ANA and anti-dsDNA antibodies after IFX initiation in case of psoriasis and rheumatoid arthritis [32,37,38]. In these previous studies, a small number of patients had lupus-like symptoms [39][40][41].…”

“…It was reported that development of ANA and anti-dsDNA antibodies is seen during the course of anti-TNF- therapy in patients with some autoimmune diseases such as rheumatoid arthritis [32][33][34], psoriasis [35], Crohn's disease [36], and BD [22]. In the present study, 75.0% of the patients converted to ANA-positive during the course of IFX therapy and positive ANA titres (1: 80) had been detected in one patient on study enrolment.…”

TNFα blockade in human diseases: Mechanisms and future directions

“…The effect of INF treatment on the induction of ANAs, anti-dsDNA, antinucleosome, antihistone, and anti-extractable nuclear antigen (anti-ENA) Abs in RA, was investigated by De Rycke et al [77]. Following treatment, there was a significant increase in the percent of RA patients that tested positive for ANAs.…”

Infliximab, but not etanercept, induces IgM anti–double‐stranded DNA autoantibodies as main antinuclear reactivity: Biologic and clinical implications in autoimmune arthritis

“…Surprisingly, the profound immunomodulation induced by TNF␣ blockers is associated with a relatively low incidence of immune-related complications such as demyelinating disease and lupus-like syndromes (3)(4)(5). This contrasts sharply with the prominent induction of autoantibodies such as antinuclear antibodies (ANAs) and anti-doublestranded DNA (anti-dsDNA) antibodies by TNF␣ blockers (6)(7)(8)(9)(10)(11)(12)(13)(14). Although this phenomenon has been recognized for several years, the clinical and biologic correlates of this antibody induction in autoimmune arthritis are not yet fully understood.…”