TY - JOUR
T1 - Analyses of plasma inflammatory proteins reveal biomarkers predictive of subsequent development of giant cell arteritis
T2 - a prospective study
AU - Wadström, Karin
AU - Jacobsson, Lennart T.H.
AU - Mohammad, Aladdin J.
AU - Warrington, Kenneth J.
AU - Matteson, Eric L.
AU - Jakobsson, Magnus E.
AU - Turesson, Carl
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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-γwas 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-γlevels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.
AB - 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-γwas 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-γlevels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.
KW - GCA
KW - IFN-γ
KW - biomarkers
KW - inflammation
KW - pathogenesis
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U2 - 10.1093/rheumatology/keac581
DO - 10.1093/rheumatology/keac581
M3 - Article
C2 - 36255228
AN - SCOPUS:85143072450
SN - 1462-0324
VL - 62
SP - 2304
EP - 2311
JO - Rheumatology (United Kingdom)
JF - Rheumatology (United Kingdom)
IS - 6
ER -