Performance Characteristics of Anti-Collagen II Antibodies in Relapsing Polychondritis and Related Diseases: Prospective Analysis, Systematic Review, and Meta-Analysis.

Abstract

Relapsing polychondritis (RP) is a rare disease defined by recurrent cartilaginous inflammation. Anti-collagen II (Col2) antibodies have been proposed as a diagnostic biomarker for RP, but their performance characteristics are not well defined. In an observational cohort, anti-Col2 antibody levels were measured in patients with RP compared to other inflammatory diseases that mimic RP. In parallel, a systematic review and meta-analysis was performed to assess anti-Col2 antibody prevalence across a broad spectrum of diseases. Individual study risk ratios (RRs) and pooled disease category RRs, study bias, and interstudy heterogeneity were assessed. In the observational cohort, anti-Col2 antibody prevalence did not differ between RP and comparators. The performance characteristics of anti-Col2 to diagnose RP were poor (sensitivity = 18%; specificity = 72%). Anti-Col2 antibody titers did not correlate with disease activity in RP (r = 0.08, P = 0.44). In the systematic review, 71 of 2,443 reviewed articles were included. Anti-Col2 antibodies were not associated with RP across five pooled studies (RR: 2.09; 95% confidence interval [CI]: 0.05-81.80; P = 0.69). Anti-Col2 antibodies were significantly associated with a composite group of inflammatory diseases with cartilaginous involvement (RR: 2.99; 95% CI: 1.29-6.91; P = 0.01). Studies using healthy controls reported increased effect sizes compared to studies that used disease controls (β-estimate = 1.14, I² = 17.08%; P = 0.0004). Anti-Col2 antibodies are neither sensitive nor specific for RP, are detected in the minority of patients with RP, and are detected at similar prevalences across a spectrum of inflammatory diseases with cartilage inflammation. Use of these antibodies to diagnose or monitor RP is not advisable.