Associations between plasma metabolism-associated proteins and future development of giant cell arteritis: results from a prospective study

Author:

Wadström Karin12ORCID,Jacobsson Lennart T H13ORCID,Mohammad Aladdin J45ORCID,Warrington Kenneth J6ORCID,Matteson Eric L6,Jakobsson Magnus E7,Turesson Carl14ORCID

Affiliation:

1. Rheumatology, Department of Clinical Sciences, Lund University , Malmö, Sweden

2. Center for Rheumatology, Academic Specialist Center , Region Stockholm, Stockholm, Sweden

3. Department of Rheumatology & Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gotherburg , Gothenburg, Sweden

4. Department of Rheumatology, Skåne University Hospital , Malmö, Sweden

5. Department of Medicine, University of Cambridge , Cambridge, UK

6. Division of Rheumatology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA

7. Department of Biomedical Science, Faculty of Health and Society, Malmö University , Malmö, Sweden

Abstract

Abstract Objective The aim of this study was to investigate the relationship between biomarkers associated with metabolism and subsequent development of GCA. Method Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30 447) who were subsequently diagnosed with GCA were identified in a structured process. Matched GCA-free controls were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics metabolism panel (92 metabolic 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 explained the variance in the proteome. Results There were 95 cases with a confirmed incident diagnosis of GCA (median 12.0 years after inclusion). Among biomarkers with a priori hypotheses, adhesion G protein-coupled receptor E2 (ADGRE2) was positively associated [odds ratio (OR) per S.D. 1.67; 95% CI 1.08–2.57], and fructose-1,6-bisphosphatase 1 (FBP1) was negatively associated (OR per S.D. 0.59; 95% CI 0.35–0.99) with GCA. In particular, ADGRE2 levels were associated with subsequent GCA in the subset sampled <8.5 years before diagnosis. For meteorin-like protein (Metrnl), the highest impact on the risk of GCA was observed in those patients sampled closest to diagnosis, with a decreasing trend with longer time to GCA (P = 0.03). In the hypothesis-generating analyses, elevated levels of receptor tyrosine-like orphan receptor 1 (ROR1) were associated with subsequent GCA. Conclusion Biomarkers identified years before clinical diagnosis indicated a protective role of gluconeogenesis (FBP1) and an association with macrophage activation (ADGRE2 and Metrnl) and proinflammatory signals (ROR1) for development of GCA.

Funder

Swedish Research Council

Lund University

King Gustav V 80-year Foundation

Swedish Rheumatism Association

Greta and Johan Kock Foundation

Publisher

Oxford University Press (OUP)

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