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Serum Metabolomic Profiling of Patients with Non-Infectious Uveitis.

ABSTRACT: 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 (Beh?et'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.

SUBMITTER: Shimizu H

PROVIDER: S-EPMC7762156 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Serum Metabolomic Profiling of Patients with Non-Infectious Uveitis.

Shimizu Hiroyuki H Usui Yoshihiko Y Asakage Masaki M Nezu Naoya N Wakita Ryo R Tsubota Kinya K Sugimoto Masahiro M Goto Hiroshi H

Journal of clinical medicine 20201206 12

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, a ...[more]

PMID: 33291298

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Project description:Non-infectious uveitis are intraocular inflammatory conditions caused by dysregulated activation of the immune response without any detectable infectious agents. The aim of this study was to explore potential markers and therapeutic targets for two distinct types of non-infectious uveitis associated with Behçet's disease (BD) and Vogt Koyanagi Harada (VKH) disease. Concentrations of 27 cytokines were investigated in aqueous humor (AH) samples from patients with active uveitis vs. healthy controls (HC) (n = 10 patients with BD-associated uveitis; n = 10 patients with VKH-associated uveitis; n = 10 HC) using the Bio-Plex ProTM human cytokine group I panel. Additionally, leukocytes in AH samples were counted with hemocytometers and characterized by flow cytometry. Eleven cytokines were differentially expressed between patients with uveitis and HC with a median concentration greater than 10 pg/ml. IL-6, IP-10, G-CSF, and IFN? showed higher concentrations in AH samples from both BD and VKH patients while IL-2, IL-8, IL-13, TNF?, eotaxin, IL-1ra showed statistically significant higher concentrations only in AH samples from BD patients. GM-CSF was the sole cytokine with an opposite profile showing decreased levels in AH samples from BD patients. IL-1ra and IL-6 were detected at higher frequencies in AH samples from BD and VKH patients compared with those from HC while IFN? and TNF? were not detected in HC. The concentrations of IL-6, IL-8, IP-10, G-CSF, IFN?, TNF?, eotaxin, IL-1ra positively correlated with the concentrations of leukocytes in AH, suggesting that such cytokines can be produced by immune cells and/or attract and/or promote proliferation and survival of immune cells in these types of uveitis. The correlation matrix of cytokine concentrations in AH samples revealed that IFN?, TNF?, eotaxin, IL-6, G-CSF highly correlated each other. The ratios of cytokine concentrations between AH and plasma intra-individuals showed that IL-2, IL-6, IP-10, GM-CSF were increased intraocularly. In conclusion, AH sampling followed by multiplex analysis of cytokines should be fostered in non-infectious uveitis to identify cytokines dysregulated intraocularly in each individual laying the groundwork for precision medicine.

Project description:Uveitis is a generic term for inflammation of the uvea, which includes the iris, ciliary body, and choroid. Prevalence of underlying non-infectious uveitis varies by race and region and is a major cause of legal blindness in developed countries. Although the etiology remains unclear, the involvement of both genetic and environmental factors is considered important for the onset of many forms of non-infectious uveitis. Major histocompatibility complex (MHC) genes, which play a major role in human immune response, have been reported to be strongly associated as genetic risk factors in several forms of non-infectious uveitis. Behçet's disease, acute anterior uveitis (AAU), and chorioretinopathy are strongly correlated with MHC class I-specific alleles. Moreover, sarcoidosis and Vogt-Koyanagi-Harada (VKH) disease are associated with MHC class II-specific alleles. These correlations can help immunogenetically classify the immune pathway involved in each form of non-infectious uveitis. Genetic studies, including recent genome-wide association studies, have identified several susceptibility genes apart from those in the MHC region. These genetic findings help define the common or specific pathogenesis of ocular inflammatory diseases by comparing the susceptibility genes of each form of non-infectious uveitis. Interestingly, genome-wide association of the interleukin (IL)23R region has been identified in many of the major forms of non-infectious uveitis, such as Behçet's disease, ocular sarcoidosis, VKH disease, and AAU. The interleukin-23 (IL-23) receptor, encoded by IL23R, is expressed on the cell surface of Th17 cells. IL-23 is involved in the homeostasis of Th17 cells and the production of IL-17, which is an inflammatory cytokine, indicating that a Th17 immune response is a common key in the pathogenesis of non-infectious uveitis. Based on the findings from the immunogenetics of non-infectious uveitis, a personalized treatment approach based on the patient's genetic make-up is expected.

Dataset Information

Serum Metabolomic Profiling of Patients with Non-Infectious Uveitis.

Publications

Serum Metabolomic Profiling of Patients with Non-Infectious Uveitis.

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