Plasma metabolomics study of Vogt-Koyanagi-Harada disease identifies potential diagnostic biomarkers

Lin, Chen; Chang, Ruijie; S, Pan; Xu, Jing; Cao, Qingfeng; Su, Guannan; Zhou, Chunjiang; Kijlstra, Aize; Yang, Peizeng

doi:10.1016/j.exer.2020.108070

Cited by 18 publications

(18 citation statements)

References 51 publications

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“…Pathway enrichment analysis showed that the altered glycine, serine and threonine metabolism and arginine and proline metabolism were evidenced by decreased guanidoacetic acid in VKH disease. Our previous plasma metabolomics study also revealed a dysregulated glycine, serine and threonine metabolism in VKH disease (Chen et al, 2020). These findings suggest that glycine, serine, and threonine metabolism may play a role in the immunopathogenesis of VKH disease.…”

Section: Discussionsupporting

confidence: 53%

“…Several uveitis entities, including VKH, also have a systemic involvement and disease activity might be reflected by urine metabolite composition. The current study on urine is an extension of our earlier metabolomics studies in VKH where we used sweat and plasma as a biological source (Chen et al, 2020;Cui et al, 2020). In this study we revealed significant differences in urine metabolite composition between VKH patients and healthy controls or between active VKH and inactive VKH patients.…”

Section: Discussionmentioning

confidence: 62%

“…The 26 enrolled VKH patients included 15 active and 11 inactive VKH patients. Active patients were those with evident inflammatory symptoms in either the anterior or posterior segment, as described elsewhere (Jabs et al, 2005;Chen et al, 2020). Details of the patients are shown in Table 1.…”

Section: Participantsmentioning

confidence: 99%

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Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease

Chang

Zhu

et al. 2021

Front. Cell Dev. Biol.

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The diagnosis of Vogt-Koyanagi-Harada (VKH) disease is mainly based on a complex clinical manifestation while it lacks objective laboratory biomarkers. To explore the potential molecular biomarkers for diagnosis and disease activity in VKH, we performed an untargeted urine metabolomics analysis by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Through univariate and multivariate statistical analysis, we found 9 differential metabolites when comparing VKH patients with healthy controls, and 26 differential metabolites were identified when comparing active VKH patients with inactive VKH patients. Pathway enrichment analysis showed that glycine, serine and threonine metabolism, and arginine and proline metabolism were significantly altered in VKH versus healthy controls. Lysine degradation and biotin metabolism pathways were significantly altered in active VKH versus inactive VKH. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that the combination of acetylglycine and gamma-glutamylalanine could differentiate VKH from healthy controls with an area under the curve (AUC) of 0.808. A combination of ureidopropionic acid and 5′-phosphoribosyl-5-amino-4-imidazolecarboxamide (AICAR) had an excellent AUC of 0.958 for distinguishing active VKH from inactive VKH. In summary, this study identified abnormal metabolites in urine of patients with VKH disease. Further studies are needed to confirm whether these metabolites are specific for this disease.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 62%

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Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease

Chang

Zhu

et al. 2021

Front. Cell Dev. Biol.

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“…Thus, we tried to explore novel biomarkers showing discrimination ability among these three diseases. Although several previous studies analysed serum metabolites, all these studies compared patients having a particular disease with HCs [18][19][20]. To our knowledge, this study represents the first time the three diseases are compared.…”

Section: Discussionmentioning

confidence: 99%

“…NMR with principal component analysis (PCA) has been used to analyse serum samples to discriminate sarcoidosis patients from HCs [19]. Plasma samples collected from VKH patients have been analysed using liquid chromatography (LC)-MS with PCA and orthogonal partial least square discriminant analysis (OPLS-DA) to differentiate these patients from HCs [20]. All these studies have aimed to distinguish patients with a particular type of uveitis from HCs, whereas methods to differentiate different types of uveitis patients from each other have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Serum Metabolomic Profiling of Patients with Non-Infectious Uveitis

Shimizu

Usui

Asakage

et al. 2020

JCM

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The activities of various metabolic pathways can influence the pathogeneses of autoimmune diseases, and intrinsic metabolites can potentially be used to diagnose diseases. However, the metabolomic analysis of patients with uveitis has not yet been conducted. Here, we profiled the serum metabolomes of patients with three major forms of uveitis (Behҫet’s disease (BD), sarcoidosis, and Vogt-Koyanagi-Harada disease (VKH)) to identify potential biomarkers. This study included 19 BD, 20 sarcoidosis, and 15 VKH patients alongside 16 healthy control subjects. The metabolite concentrations in their sera were quantified using liquid chromatography with time-of-flight mass spectrometry. The discriminative abilities of quantified metabolites were evaluated by four comparisons: control vs. three diseases, and each disease vs. the other two diseases (such as sarcoidosis vs. BD + VKH). Among 78 quantified metabolites, 24 kinds of metabolites showed significant differences in these comparisons. Four multiple logistic regression models were developed and validated. The area under the receiver operating characteristic (ROC) curve (AUC) in the model to discriminate disease groups from control was 0.72. The AUC of the other models to discriminate sarcoidosis, BD, and VKH from the other two diseases were 0.84, 0.83, and 0.73, respectively. This study provides potential diagnostic abilities of sarcoidosis, BD, and VKH using routinely available serum samples that can be collected with minimal invasiveness.

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Bench-to-Bedside Research in Ophthalmology

Gupta

2022

Biomedical Translational Research

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Plasma metabolomics study of Vogt-Koyanagi-Harada disease identifies potential diagnostic biomarkers

Cited by 18 publications

References 51 publications

Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease

Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease

Serum Metabolomic Profiling of Patients with Non-Infectious Uveitis

Bench-to-Bedside Research in Ophthalmology

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