IgA anti-CD74 autoantibodies are associated with treatment escalation in peripheral psoriatic arthritis.

Background: Psoriatic arthritis (PsA) often requires escalation from conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to biologic therapy (bDMARDs), yet biomarkers guiding treatment decisions remain limited. Anti-CD74 autoantibodies have shown diagnostic potential in axial spondyloarthritis, but their relevance in PsA is insufficiently characterized. Objective: To evaluate whether IgA anti-CD74 levels are associated with treatment escalation in peripheral PsA (pPsA) and to characterize their relationships with clinical and immunological parameters. Methods: Serum samples from 171 PsA (127 pPsA, 44 axial PsA [axPsA]), 43 non-rheumatic disease controls (NRD), and 43 rheumatoid arthritis (RA) patients were analyzed. IgA anti-CD74 levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients were stratified by disease duration and treatment exposure. Correlation analyses, receiver operating characteristic (ROC) curves, and logistic regression models were performed. A prospective subgroup of 53 early pPsA patients was followed to assess treatment initiation. Results: IgA anti-CD74 levels were elevated in PsA compared with NRD controls (median 13 vs. 6 U/mL, p < 0.0001), with similar levels in pPsA and axPsA and comparable values in RA, indicating an association with inflammatory disease rather than disease specificity. Anti-CD74 positivity (>15 U/mL) was observed in 31.5% of pPsA and 43.2% of axPsA versus 2.3% of NRD, independent of disease duration. Anti-CD74 levels were associated with treatment escalation in pPsA, with higher levels in bDMARD-treated patients (median 13.0 vs. 11.0 U/mL, p = 0.04). In multivariate analyses, anti-CD74 was independently associated with csDMARD (OR 1.113, p = 0.022) and bDMARD use (OR 1.052, p = 0.02). After false discovery rate (FDR) correction, anti-CD74 remained associated with serum IgA (q = 0.0008) and weakly with IgG (q = 0.0250), but not with C-reactive protein (CRP) or age. Longitudinal associations were not significant after FDR correction (csDMARD initiation: p = 0.047, q = 0.094; bDMARD initiation: p = 0.19, q = 0.1866), indicating these findings are exploratory. Conclusion: IgA anti-CD74 levels are elevated in PsA and appear to reflect immunological activity not captured by CRP. Their independent association with treatment escalation in pPsA supports further evaluation as a biomarker candidate, although findings remain exploratory and require validation in larger longitudinal cohorts.