Background/Purpose: Rheumatoid arthritis (RA) is characterized by polyarticular synovitis and frequent occurrence of autoantibodies, playing a central role in disease progression. Anti-citrullinated peptide antibodies (ACPA) are associated with periodontitis, smoking and upper respiratory tract infections, suggesting a breach of tolerance on mucosal surfaces. Early and aggressive treatment is important to limit long-term disease severity in RA, and seropositivity for APCA IgG is generally considered to be associated with a more aggressive disease. Here, we report the seroprevalence of ACPA IgA and its subtypes in patients with early (e), untreated RA and their association with long-term radiographic outcome.

Methods: The patients (n=121) included in this post hoc analysis participated in the investigator-initiated, double-blinded, placebo-controlled CIMESTRA study were treated with methotrexate and intraarticular glucocorticoids cyclosporin according to a treat-to-target protocol (Scand J Rheumatol 2018, 48: 1-8). Patient characteristics, IgM rheumatoid factor (IgM-RF) and IgG ACPA were recorded at baseline. Disease activity parameters included C-reactive protein (CRP), health assessment questionnaire (HAQ) and visual analogue scale (VAS), Disease Activity Score in 28 joints (DAS28) and swollen joint count in 28 joints (SJC28). Furthermore, structural joint damage was assessed with van der Heijde modified Total Sharp Score (TSS). All parameters were assessed at baseline and after 2 and 11 years. Total IgA, IgA1 and IgA2 ACPA were measured by ELISA at baseline and after 2 years. Statistical analyses and graphs were done using Prism 9 (GraphPad, Software). Correlations were tested using Spearman’s rho (ρ).

Results: At baseline and after two years’ treatment, total IgA, IgA1 and IgA2 ACPA were detectable in serum. Levels did not differ between baseline and 2 years. Baseline levels of ACPA IgA was associated to: IgG ACPA (ρ = 0.62), IgM rheumatoid factor (ρ = 0.37), gender (ρ = 0.24) and tender joints (ρ = -0.20), all p-values < 0.05. We considered a change in TSS ≥ 5 as significant radiographic progression. Using this cutoff, high baseline levels of total serum IgA (AUC = 0.71, p = 0.002) and IgA1 ACPA (AUC = 0.65, p = 0.03) predicted increased radiographic changes after 11 years, while IgA2 did not (p = 0.12). High baseline levels of total serum IgA (AUC = 0.70, p = 0.001) or IgA1 ACPA (AUC = 0.64, p = 0.026) also predicted high ΔTSS score ( > 5). By contrast, total serum IgG ACPA did not predict a worsening of neither TSS (p = 0.67) nor ΔTSS (p = 0.37) after 11 years (Figure 1).

Conclusion: Our study confirms a role for IgA ACPA in patients with eRA and indicate that seropositivity for IgA ACPA is associated with a poor 11-year radiographic outcome in patients with eRA as measured by TSS. ACPA IgA and IgA1 are superior to ACPA IgG in predicting long-term rapid radiographic progression suggesting that there is a potential clinical gain by measuring ACPA IgA-subclasses in patients with eRA.

ROC curves showing sensitivity vs specificity for IgA ACPA and IgG ACPA. Panel A shows data from TSS, and panel B shows data from ∆TSS. A cut-off value for no radiographic changes was set to 5.

« Back to ACR Convergence 2021

ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-levels-of-total-iga-anti-cyclic-citrullinated-protein-antibodies-predict-11-year-radiographic-outcome-in-early-rheumatoid-arthritis/