Plasma metabolomics reveals distinct metabolic alterations and biomarkers of disease activity in HLA-B27-positive acute anterior uveitis.

HLA-B27 positivity is strongly associated with acute anterior uveitis (AAU). This study investigated HLA-B27-dependent metabolic alterations in AAU and identified potential biomarkers of disease activity using plasma metabolomics. Untargeted and targeted metabolomics were employed to compare plasma metabolic profiles of HLA-B27-positive and negative patients. Distinct metabolic signatures, characterised by significant alterations in pyruvic acid and L-kynurenine, were identified in HLA-B27-positive individuals compared to HLA-B27-negative individuals. Furthermore, citric acid levels in these HLA-B27-positive patients correlated significantly with disease activity, particularly in those not receiving systemic medication. Pathway analysis revealed significant differences between HLA-B27-positive and negative patients in several key metabolic pathways, including the citrate cycle, tryptophan metabolism, pyruvate metabolism, and glycolysis/gluconeogenesis. A diagnostic model with citric acid alongside C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) demonstrated improved performance in predicting disease activity compared to a model utilising CRP and ESR alone (AUC: 0.727 vs. 0.713 and 0.674 vs. 0.670 in the untargeted and targeted cohorts, respectively). These findings offer insights into the metabolic dysregulation associated with HLA-B27-positive AAU and suggest that citric acid may be a potential biomarker for assessing disease activity, warranting further validation.