THU0064 ANTIBODY-RESPONSE MATURATION IN THE PHASE OF CLINICALLY SUSPECT ARTHRALGIA AND ITS RELATION WITH PROGRESSION TO RHEUMATOID ARTHRITIS
Authors: F. Wouters, E. Niemantsverdriet, N. Salioska, A. L. Dorjée, R. Toes, A. Van der Helm - van Mil
Journal: Annals of the Rheumatic Diseases (2020)

Background: Auto-antibodies in rheumatoid arthritis (RA) are often present years before disease onset but their mere presence does not seem enough to induce RA. Because several nested-case control studies have shown that autoantibody-response maturation precedes disease onset, it is suggested that it plays a role in disease triggering. At present, it is undetermined whether autoantibody-response maturation occurs in the symptomatic phase preceding clinical arthritis (i.e. Clinically Suspect Arthralgia, CSA), or whether it occurs even earlier in the asymptomatic phase. Secondly, if autoantibody-response maturation is a final step towards clinical disease development, maturation is expected to be present in the patients that progress from CSA to RA, but not in CSA-patients that do not progress. Objectives: To better understand the timeframe of autoantibody-response maturation and its relation to development of RA, we investigated autoantibody-response maturation in patients with CSA that did and did not progress to clinically apparent inflammatory arthritis (IA). Methods: In serum from 148 CSA-patients, we determined the presence and levels of three autoantibodies (ACPA, anti-CarP and AAPA), with three isotypes each (IgM, IgG, IgA), resulting in 9 autoantibody measurements per patient per time-point. Measurements were performed on sera obtained at first presentation at the outpatient clinic and when patients developed IA or else after two years. In-house ELISA was used for all measurements. Three analyses were performed, in patients that progressed to IA (n=56) and in patients that did not progress (n=92) separately. First, in patients negative for all measurements at baseline, we determined the frequency of conversion to seropositivity. Second, in patients with at least one positive test at baseline, we studied the frequency of autoantibody positivity over time. Finally, we determined the change in autoantibody levels in patients positive for the respective autoantibodies at baseline. Frequencies and medians were reported. Statistical significance was tested with Fisher’s Exact test and GEE, taking into account that measurements within one autoantibody type (ACPA, anti-CarP or AAPA) can be correlated. Results: First we studied patients negative for all antibodies at baseline (54% of patients that progressed to IA and 76% of patients that did not progress). 17% of patients that progressed to IA became positive over time, compared to 6% of the patients that did not develop IA (p=0.12). Then we studied patients in whom at least one autoantibody was present at baseline and evaluated autoantibody-positivity over time. In patients that progressed to IA, the number of autoantibodies detected at baseline did not change significantly during follow-up (median 1.5 (IQR 1-3, max. 6) to 1.0 (IQR 1-4, max. 6) (p=0.18)). In the patients with CSA that did not progress similar findings were made (1.0 (IQR 1-2, max. 4) at baseline and 1.0 (IQR 0-2, max. 5) after 2-years (p=0.07)). Increase in number of positive measurements over time took place in only few patients: in 15% of the patients that progressed to IA and in 18% from those that did not progress (p=1.00). Likewise, autoantibody levels did not significantly change over time, both in patients that progressed and in patients that did not progress. Conclusion: The presence of IgM, IgG and IgA ACPA, anti-CarP and AAPA, as well as autoantibody levels, did not significantly increase over time in patients with CSA; this was similar for patients that did and did not develop clinical arthritis. These findings suggest that antibody-response maturation occurs before presenting with symptoms and also that broadening of the autoantibody response is not specific for progression from arthralgia to RA. Disclosure of Interests: None declared