Analyses of plasma inflammatory proteins reveal biomarkers predictive of subsequent development of giant cell arteritis: a prospective study

OBJECTIVE: To investigate the relation between biomarkers of inflammation and subsequent development of giant cell arteritis (GCA).

METHOD: Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30447), established 1991-1996, who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth, and year of screening were selected from the study cohort. Baseline plasma samples were analyzed using the antibody-based OLINK proteomics inflammation panel (92 inflammatory proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. Within components selected based on Eigenvalues, proteins with a factor loading of > 0.50 were investigated.

RESULTS: 94 cases with a confirmed incident diagnosis of GCA (median 11.9 years after inclusion) were identified. Among biomarkers with a priori hypotheses, IFN-γ was positively associated with GCA (odds ratio (OR) per SD 1.52; 95% CI 1.00-2.30). Eight biomarkers in the hypothesis-generating analyses were significantly associated with development of GCA. Among these, higher levels of IFN-γ (OR 2.37; 95% CI 1.14-4.92) and MCP3 (OR 4.27; 95% CI 1.26-14.53) were particularly associated with increased risk of GCA in the subset sampled <8.5 years before diagnosis. Several other proteins known to be important for T cell function were also associated with GCA in these analyses, e.g. CXCL9, IL-2, CD40 and CCL25.

CONCLUSION: Elevated IFN-γ levels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.