Date: Monday, October 22, 2018
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) are the most specific diagnostic markers of rheumatoid arthritis (RA). Lately we showed that the determination of multiple isotypes of RF and ACPA as well as RA33 antibodies may provide an added diagnostic value since the presence of multiple reactivities in sera of RA patients as compared to disease controls was found to be highly specific for RA1. Moreover, determination of autoantibody isotypes might even provide a predictive value regarding the response to therapy. It was the aim of this study to investigate the potential predictive value of IgA, IgG and IgM isotypes of RF, ACPA and RA33 antibodies regarding therapeutic response to methotrexate (MTX) in patients with RA.
Methods: An inception cohort of 165 patients starting MTX therapy was analysed for the presence of IgA, IgG and IgM isotypes of RF and ACPA using EliATM assays (Phadia AB, Sweden). RA33 antibody isotypes were detected by newly developed prototype assays using the EliA™ platform (Phadia AB, Sweden)1. Therapeutic responses were analysed after 3-6 months using the American College of Rheumatology (ACR)20 and simplified disease activity index (SDAI)50 response criteria. For generating classification models the machine learning tool Weka was employed.
Results: Patients testing positive for four or more antibodies were found having an increased likelihood to reach an ACR20 response (41%) compared to seronegative patients (24%, p=0.0038) or patients with 1 to 3 antibody reactivities (26%, p=0.0152). Interestingly, further analyses revealed high levels of IgM-RF (>133 IU/ml) to be associated with the therapeutic response to MTX as 71% of the patients (i.e.15 of 21) achieved an ACR20 response compared to 28% of patients with IgM-RF <133 IU/ml (p<0.0001) and 27% of RF-negative patients (p<0.0001). Moreover, also the presence of RA33 antibodies was associated with a favorable MTX response since 47% of patients positive for IgG, IgA or IgM RA33 antibodies achieved an ACR20 response compared to 28% in the RA33 negative population (p=0.0005). Remarkably, by combining the RF and RA33 data a population of MTX non-responders could be characterized showing IgM-RF<133 IU/ml and IgG-RA33<3.2 µg/l since 91% of these patients (n=47) did not reach an ACR20 response compared to 58% non-responders in the total cohort (p<0.0001). Virtually identical results were obtained when SDAI50 was used as outcome measure. Interestingly, ACPA isotypes did not appear to be associated with the therapeutic response to MTX.
Conclusion: The detection of antibody isotypes especially IgM-RF and IgG-RA33 may provide valuable additional information regarding the prediction of response to MTX.
- Sieghart D et al. Determination of Autoantibody Isotypes Increases the Sensitivity of Serodiagnostics in Rheumatoid Arthritis. Front Immunol. 2018 Apr 24;9:876.
To cite this abstract in AMA style:Sieghart D, Platzer A, Alasti F, Studenic P, Grundhuber M, Swiniarski S, Blüml S, Haslacher H, Smolen JS, Steiner G. The Prognostic Value of Autoantibody Isotypes for Predicting Therapeutic Responses to Methotrexate in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/the-prognostic-value-of-autoantibody-isotypes-for-predicting-therapeutic-responses-to-methotrexate-in-patients-with-rheumatoid-arthritis/. Accessed August 25, 2019.
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