Elevated serum immunoglobulin A predicts extra-articular manifestations in axial spondyloarthritis

To determine whether serum immunoglobulin A (IgA) identifies an extra-articular-prone phenotype in axial spondyloarthritis (axSpA) and assess its clinical utility.

We retrospectively analysed 402 patients with axSpA. Elevated IgA was defined as > 4.0 g/L. Associations with extra-articular manifestations (EAMs) were evaluated by logistic regression, and time to first EAM by Kaplan-Meier and Cox models. Discrimination and clinical utility were assessed.

During follow-up, 45.5% of patients developed ≥1 EAM and 8.7% developed ≥2. Elevated IgA occurred in 15.0% overall but was more common in patients with multiple EAMs (40.6%) than in those without (10.9%) or with a single EAM (14.7%); corresponding odds ratios were 5.57 (95% CI 2.41-12.89, p < 0.001) and 3.98 (1.66-9.54). Elevated IgA predicted ≥2 EAMs with 40.6% sensitivity, 89.0% specificity, and an area under the curve of 0.65, rising to 0.78 when combined with C-reactive protein (CRP). Kaplan-Meier analysis showed reduced EAM-free survival with elevated IgA (p = 0.008). In Cox models, elevated IgA independently predicted incident EAMs (hazard ratio 2.28, 95% CI 1.18-4.40, p = 0.014). Decision-curve analysis indicated a positive net benefit. Crohn's disease was overrepresented among patients with elevated IgA (33.3% vs 11.4%, p < 0.0001).

Elevated serum IgA delineates an intestinally biased, extra-articular-prone axSpA phenotype and provides actionable information beyond CRP, supporting the integration of IgA-based risk stratification into EAM surveillance.