Background 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) 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 (1, 2).
Objectives So far, published data on anti-RA33 antibodies refer only to the IgG isotype. It was therefore the aim of this study to measure the prevalence of anti-RA33 IgG, IgM and IgA antibodies in patients with RA and to determine their potential prognostic value regarding prediction of response to treatment.
Methods A total of 255 patients were tested for the presence of IgG, IgM and IgA anti-RA33 antibodies by a newly developed EliA® (Thermo Fisher Scientific). All patients had initially been treated with conventional synthetic drugs (mostly methotrexate) and were subsequently treated with at least one TNF inhibitor. Therapeutic responses to MTX and TNF blocking biologicals were calculated 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)50 and American College of Rheumatology (ACR)20 responses were calculated.
Results Among the 255 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 anti-TNF therapy (Figure 1A), in the group of patients testing positive for anti-RA33 antibodies of any isotype (with or without concomitant RF and/or ACPA) the percentage of SDAI50 responders (24%) was significantly lower (p=0.0117) 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 (Figure 1B) the percentage of SDAI50 responders was significantly higher (p<0.0001) among anti-RA33 positive patients (with or without RF and/or ACPA) (59% responders) compared to anti-RA33 negative (but RF/ACPA positive) patients (37% responders) and seronegative patients (24% responders).
Conclusions In agreement with previous findings (1,2) anti-RA33 antibodies reduced the diagnostic gap left by ACPA and RF and thus the percentage of seronegative patients by 13%. Importantly, the presence of anti-RA33 antibodies was associated with a favourable response to MTX on the one hand and with a diminished response to TNF inhibitors on the other hand. Therefore, these antibodies appear to have some prognostic value for prediction of therapeutic responses and could become helpful tools in therapeutic decision making.
Nell VPK, Machold KM, Stamm TA, et al. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis 2005, 64:1731–6.
Yand X, Wang M, Zhang X et al. Diagnostic accuracy of anti-RA33 antibody for rheumatoid arthritis: systematic review and meta-analysis. Clin Exp Rheumatol. 2016; 34:539–47.
Disclosure of Interest G. Steiner Consultant for: Phadia Austria GmbH, Thermo Fisher Scientific, D. Sieghart: None declared, P. Studenic: None declared, T. Horn Employee of: Phadia Austria GmbH, Thermo Fisher Scientific, D. Aletaha: None declared, J. Smolen: None declared