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

• Published in: Rheumatology (Oxford, England) Vol. 62; no. 6; pp. 2304 - 2311
• Main Authors: Wadström, Karin, Jacobsson, Lennart T H, Mohammad, Aladdin J, Warrington, Kenneth J, Matteson, Eric L, Jakobsson, Magnus E, Turesson, Carl
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.06.2023
• Subjects: activation; Basic Medicine; Basic Science; biomarkers; body-mass index; Cell and Molecular Biology; Cell- och molekylärbiologi; cxcl10; disease-activity; expression; GCA; IFN-gamma; inflammation; interferon-gamma; interleukin-6; mechanisms; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; pathogenesis; polymyalgia-rheumatica; responses; Reumatologi och inflammation; Rheumatology; Rheumatology and Autoimmunity; pathogenesis; IFN-γ; GCA; inflammation; biomarkers
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/keac581

Abstract Objective To investigate the relation between biomarkers of inflammation and subsequent development of GCA. Method Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30 447), established 1991–96, 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 analysed 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 Ninety-four 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 s.d. 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 monocyte chemotactic protein 3 (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.