Background/Purpose:

The production of autoantibodies, such as anti-nuclear antibodies (ANA) and anti-ds DNA antibodies (anti-DNA), is commonly observed in patients who have been treated with tumor necrosis factor (TNF) inhibitors. We had reported that accelerated anti-DNA production was predominantly observed in patients treated with infliximab (IFX), and this occurred more frequently in anti-Ro/SS-A antibodies (anti-Ro) positive rheumatoid arthritis (RA) patients. The purposes of this study were to examine whether the positive rate of ANA and anti-DNA before and after commencement of treatment is different among TNF inhibitors and to compare the positive rates between anti-Ro-positive and -negative patients. Moreover, we investigated the relationship between the production of such autoantibodies and clinical response. 

Methods:

We examined 246 patients with RA treated with TNF inhibitors as the first biologics DMARDs: IFX; 116, etanercept (ETN); 64, adalimumab (ADA); 36, and golimumab (GLM); 30 and studied positive rate of ANA and anti-DNA before and after commencement of each TNF inhibitors. ANA was tested using an indirect immunofluorescent assay on fixed HEp-2 cell substrate. Anti-DNA was measured using a radioimmunoassay (RIA). A part of anti-DNA positive patients were tested anti-DNA isotype of IgG, IgM, and IgA by enzyme-linked immunosorbent assay. We compared the positive rate of ANA and anti-DNA between anti-Ro-positive and -negative patients. Clinical response was evaluated by EULAR response using disease activity score (DAS) 28/CRP.

Results:

The positive rate of ANA before and after commencement of IFX, ETN, ADA, and GLM were 63.8% to 89.7%, 56.3% to 68.8%, 72.2% to 75.0%, and 66.7% to 63.3%, respectively. Sixty-five patients (26.4%) were anti-DNA positive after TNF inhibitors, and anti-DNA titers increased from baseline after IFX, ETN, ADA, and GLM were 4.3% to 41.4%, 1.6% to 10.9%, 8.3% to 25.0%, and 0.0% to 3.3%, respectively. Both ANA and anti-DNA were significantly elevated after treated with IFX than other TNF inhibitors (p<0.001 and p<0.001, respectively). Moreover, the positive rate of anti-DNA in patients treated with IFX and ADA was notably increased in anti-Ro-positive patients compared to anti-Ro-negative patients (68.2% vs 35.1%; p=0.009, 66.7% vs 16.7%; p=0.039, respectively). On the other hand, only one patient was anti-DNA positive after  treated with GLM and there was no anti-Ro-positive patient who anti-DNA was detected after treated with GLM. In 38 patients with positive anti-DNA by RIA, isotype of IgM was found in 34 cases (89.5%) after treatment, while IgG and IgA was positive in few patients. Furthermore, 35 of 65 patients increased anti-DNA after treated with TNF inhibitors were stopped or switched biologics because of inefficacy and this observation was found in most of the patients with anti-Ro (71.4%). 

Conclusion:

The production of anti-DNA after treated with TNF inhibitors was frequently increased in anti-Ro-positive patients and it was suggested to relate to the lesser clinical response and to decrease the continuation rate. In addition, the production of autoantibodies was different among TNF inhibitors and it might be considered to select the treatment of TNF inhibitors.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/study-of-the-production-of-antinuclear-antibodies-and-anti-ds-dna-antibodies-in-rheumatoid-arthritis-patients-treated-with-tnf-inhibitors/