Background/Purpose:

Besides the determination of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), anti-RA33 antibodies (which are directed to the nuclear antigen hnRNP-A2/B1) could be of additional diagnostic and/or prognostic value in patients with rheumatoid arthritis (RA) because they are also found in RF/ACPA negative patients.

Methods:

To determine the diagnostic sensitivity and specificity of anti-RA33 subtypes sera from 255 RA patients, 258 disease controls and 100 healthy subjects were tested by a prototype anti-RA33 EliA® (Thermo Fisher Scientific) for the presence of anti-RA33 IgG, IgA and IgM antibodies. ACPA and RF were routinely measured by EliA® and nephelometry, respectively. All RA patients had initially been treated with conventional synthetic drugs (mostly methotrexate, MTX) and were subsequently treated with at least one TNF inhibitor (TNFi). Therapeutic responses to MTX and TNF blocking biologicals were analyzed in an inception cohort (n=104) who had started their DMARD therapy at our clinic. To define therapeutic responses the simplified disease activity index (SDAI) and American College of Rheumatology (ACR) responses were calculated.

Results:

Diagnostic specificity was >96% for all 3 anti-RA33 subtypes. Among the 255 RA patients, 11% tested positive for anti-RA33 IgG antibodies, 15% for IgM antibodies and 6% for IgA antibodies. Altogether, 62 patients (24%) had at least one type of anti-RA33 antibody: 24 patients were RF-negative, 26 were ACPA-negative and 18 were RF/ACPA double negative. Thus, in 32 patients (13%), anti-RA33 was the only antibody specificity. Regarding response to therapy, the percentage of SDAI50 responders (24%) was significantly lower (p=0.0117) in the group of patients testing positive for anti-RA33 antibodies of any isotype (with or without concomitant RF and/or ACPA) than in anti-RA33 negative (but RF/ACPA positive) patients (42% responders) and similar to the group of completely seronegative patients (21% responders). In contrast, regarding responses to MTX the percentage of SDAI50 responders was significantly higher (p<0.0001) among anti-RA33 positive patients (with or without cocomitant RF and/or ACPA) (59% responders) compared to anti-RA33 negative (but RF/ACPA positive) patients (37% responders) and seronegative patients (24% responders).

Conclusion:

Apart from their added diagnostic value anti-RA33 antibodies of any isotype may have also prognostic value for prediction of therapeutic responses to MTX and TNFi treatment. Therefore anti-RA33 antibodies may be taken into consideration as additional diagnostic and prognostic markers that might become helpful tools in therapeutic decision making.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-ra33-hnrnp-a2b1-autoantibodies-are-associated-with-the-therapeutic-response-to-methotrexate-and-anti-tnf-treatment-in-patients-with-rheumatoid-arthritis/