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

Eye (2026)Cite this article

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Abstract

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.

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Fig. 1: HLA-B27-dependent metabolic differences in discovery and validation cohorts.
Fig. 2: Pyruvic acid and L-Kynurenine are consistently altered in HLA-B27-Positive AAU.
Fig. 3: Association of pyruvic acid and L-kynurenine with ocular inflammation in HLA-B27-positive AAU patients stratified by systemic medication and disease activity.
Fig. 4: Citric acid levels and metabolic pathway analysis in HLA-B27-positive AAU.
Fig. 5: Correlation of citric acid with anterior chamber cell count and diagnostic model performance.

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Data availability

The clinical datasets supporting this study are restricted due to ethical and legal constraints. However, qualified researchers affiliated with academic institutions may apply for access by contacting corresponding author. Data release is subject to proposal approval by the management committee and the execution of a formal data access agreement.

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Funding

Supported by 82025009, 80220071 from The National Natural Science Foundation of China.

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Author notes

  1. These authors contributed equally: Kai Wang, Xiwen Ji.

Authors and Affiliations

  1. State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China

    Kai Wang, Xiwen Ji, Bintao Xie, Mengmeng Dong, Yabin Tang, Ruyi Chen, Hao Wu, Jia Qu & Xiangtian Zhou

  2. Research Unit of Myopia Basic Research and Clinical Prevention and Control, Chinese Academy of Medical Sciences, Wenzhou, Zhejiang, China

    Hao Wu & Xiangtian Zhou

  3. Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China

    Hao Wu, Jia Qu & Xiangtian Zhou

  4. National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China

    Hao Wu, Dan Lin, Xingneng Guo, Ruru Liu, Jia Qu, Yuqin Wang & Xiangtian Zhou

  5. Beijing Anzhen Hospital, Capital Medical University, Beijing, China

    Jie Du

  6. Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China

    Jie Du

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Contributions

XZ, JD, JQ, and YW contributed to the design of the clinical cohorts. KW, XJ, BX, MD, YT, RC, HW, DL, XG, and RL contributed to the collection of blood samples and clinical information. KW and XJ performed data analyses. XZ and JD contributed to statistical guidance and review. KW and XJ wrote the manuscript. XZ and JD guided the study and approved the final version.

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Correspondence to Xiangtian Zhou.

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Wang, K., Ji, X., Xie, B. et al. Plasma metabolomics reveals distinct metabolic alterations and biomarkers of disease activity in HLA-B27-positive acute anterior uveitis. Eye (2026). https://doi.org/10.1038/s41433-026-04307-5

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