POS0723 ANALYSES OF PLASMA METABOLIC PROTEINS REVEAL BIOMARKERS PREDICTIVE OF SUBSEQUENT DEVELOPMENT OF GIANT CELL ARTERITIS; A PROSPECTIVE STUDY

Background Incident cases of giant cell arteritis (GCA) have a significantly reduced prevalence diabetes at time diagnosis (1) and lower fasting blood glucose, lipid levels body mass index compared to controls been found years before clinical [2,3]. This implicates metabolic pathways in the development GCA. Objectives To investigate relation between plasma proteins associated with metabolism subsequent Methods Participants population-based survey (N=30447), who were subsequently diagnosed GCA, identified structured process. GCA-free controls, matched for sex, year birth, screening selected from study cohort. Baseline samples analyzed using antibody-based OLINK proteomics panel (92 proteins). Analyses pre-designated as hypothesis-driven or hypothesis-generating. In latter, principal component analysis was used identify groups that explain variance proteome. Results There 95 confirmed incident GCA (median 11.4 after inclusion). Among biomarkers priori hypotheses, Adhesion G protein-coupled receptor E2 (ADGRE2) positively Fructose-1,6-bisphosphatase 1 (FBP1) negatively (Table 1). particular, ADGRE2 elevated subset sampled <8.5 For meteorin-like protein (Metrnl), highest impact on risk observed those closest diagnosis, decreasing trend longer (p=0.03). hypothesis generating analyses, tyrosine-like orphan (ROR1) Conclusion Our results indicate changes regulatory effects immune system might precede onset by many years. be predictive both Metrnl are macrophage activation. ROR1 mediated activation NFkB may relevant this context. The negative association FBP1, which is rate-controlling enzyme gluconeogenic pathway, compatible protective role glucose metabolites. References [1]Ungpresart P et al. Mod Rheumatol. 2016;26(3):410-4 [2]Wadström K Rheumatology (Oxford) 2020; 59 (11):3229-36 [3]Jakobsson 2015; 54 (3):433-40 Table 1. Potential arteritis, hypotheses. Overall stratified diagnosis. All Quartile (0.3-8.5 years) (N*=45) 2 (8.50-12.0 (N*=49) 3 (12.0-15.5 (N*=46) 4 (15.5-19.1 (N*=48) OR (CI) METRNL 1.42 (0.90-2.23) 2.40 (0.98-5.85) 3.13 (0.92-10.63) 0.90 (0.38-2.15) 0.74 (0.29-1.89) 0.03 FBP1 0.59 (0.35-0.99 ) 0.29 (0.06-1.39) 0.84 (0.43-1.65) 1.13 (0.38-3.30) 0.09 (0.02-0.48) 0.24 GAL 0.98 (0.66-1.45) 2.32 (0.83-6.51) 0.65 (0.29-1.49) 0.38 (0.15-0.97) 2.17 (0.92-5.13) GHRL 0.83 (0.55-1.25) 1.20 (0.52-2.78) 1.38 (0.66-2.88) 0.39 (0.16-0.96) 0.55 (0.20-1.48) 0.06 1.67 (1.08-2.57 3.91 (1.45-10.60 1.17 (0.52-2.64) 0.94 (0.44-2.00) 2.90 (0.83-10.16) 0.26 NECTIN2 1.33 (0.88-2.01) 1.47 (0.66-3.32) 1.64 (0.71-3.82) 1.40 (0.63-3.11) (0.34-2.09) *Total Conditional logistic regression hypothesis. Odds ratios (OR) per standard deviation % confidence intervals (CI). Acknowledgements: NIL. Disclosure Interests Karin Wadström: None declared, Lennart T.H. Jacobsson Consultant of: personal fees Novartis, Eli-Lily Janssen, Aladdin J Mohammad: Kenneth Warrington Chemocentryx, Grant/research support from: Support Eli-Lilly, GSK Kiniksa Mayo Clinic trials, Eric Matteson UpToDate, Magnus Jakobsson: Carl Turesson Speakers bureau: AbbVie, BMS, Nordic Drugs, Pfizer och Roche, research grant paid Lund University Bristol Myers-Squibb.