Background/Purpose: Anti-collagen II (Col2) antibodies have been clinically and experimentally associated with relapsing polychondritis (RP), rheumatoid arthritis (RA), and other diseases. Whether anti-Col2 antibodies are directly involved in disease pathogenesis in humans or represent a marker of cartilage disease remains unknown. The purpose of this study was to synthesize and evaluate the current evidence in the literature on the prevalence and diagnostic performance of anti-Col2 antibodies across all the diseases in which it has been studied.

Methods: A systematic review and meta-analysis was performed on diagnostic performance of anti-Col2 antibodies across a broad spectrum of diseases and studies in accordance with the recommendations of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The study was registered in PROSPERO (April 1, 2025; CRD# 1023286). A PubMed search for articles measuring anti-Col2 antibodies in human serum was completed using the terms ((anti-collagen II) OR (collagen II antibodies)) AND (human)). Additionally, snowballing was used to identify articles not captured in the original search. Two independent investigators classified each article into one of four categories: inflammatory diseases with cartilage involvement, inflammatory diseases without cartilage involvement, non-inflammatory diseases, and pre-RA patients. Forest, funnel, and meta-regression plots were generated to evaluate individual study risk ratios (RR) and pooled disease category RR, study bias, and inter-study heterogeneity.

Results: Out of 2443 reviewed articles, 72 were selected for analysis. Prevalence of anti-Col2 antibodies was significantly associated with the group of inflammatory diseases with cartilaginous involvement (RR 2.99; 95% CI: 1.29, 6.91; p=0.01); however, it was not significantly associated with most of the specific diseases contained in this category, including RP or RA (Figure 1). There was no significant association between anti-Col2 antibody positivity and inflammatory diseases without cartilage involvement (RR: 1.74, 95% CI: 0.84, 3.61, p = 0.138), non-inflammatory diseases (RR: 1.10, 95% CI: 0.44, 2.75, p = 0.84) or the pre-RA group (RR: 1.15, 95% CI: 0.25, 5.40, p = 0.86) (Figure 1). Studies that used healthy rather than disease controls reported increased effect sizes (Beta-estimate = 1.14, I2=17.08%, p=0.0004) (Figure 2).

Conclusion: Anti-Col2 antibodies have been indiscriminately detected in several diseases where there is inflammation of cartilage. As such, Anti-Col2 antibodies are more likely a marker of inflammatory cartilage damage rather than a driver of disease pathogenesis. Clinical use of these antibodies to diagnose specific conditions, such as RP, is not advisable.

Figure 1: Forest plots summarized by disease within each composite disease subgroup. The risk ratio (RR) is the probability of anti-col2 antibody positivity in the disease versus control groups.

Figure 2: Differences in Composition of the Control Population Explains a Proportion of Heterogeneity Between Studies

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/performance-characteristics-of-anti-collagen-ii-antibodies-for-diagnosing-inflammatory-and-non-inflammatory-diseases-a-systematic-review-and-meta-analysis/