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Clusters in Behcet's syndrome.

ABSTRACT: Clustering is an important clinical feature of Behçet's syndrome (BS) and may have pathogenetic and therapeutic implications. Recent and previous studies on BS phenotype differ substantially in terms of methodology. Correlation matrices and factor analyses were not efficient enough to uncover clusters. Clustering patterns may change according to demographic factors such as age and sex. Clustering patterns may also be profoundly influenced by the misperception of symptoms that are assumed to be secondary to BS, when, in fact, they represent manifestations of BD mimics. This can give rise to misleading conclusions and should be kept in mind when interpreting data obtained by clustering or other phenotype analyses of BS. A true geographical/racial variability in disease expression could be studied in a multinational consensus cohort. Pathogenetic studies in separate clusters of BS have still been lacking.

SUBMITTER: Ilgen U

PROVIDER: S-EPMC9617315 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Clusters in Behçet's syndrome.

İlgen Ufuk U

Arthritis research & therapy 20221029 1

Clustering is an important clinical feature of Behçet's syndrome (BS) and may have pathogenetic and therapeutic implications. Recent and previous studies on BS phenotype differ substantially in terms of methodology. Correlation matrices and factor analyses were not efficient enough to uncover clusters. Clustering patterns may change according to demographic factors such as age and sex. Clustering patterns may also be profoundly influenced by the misperception of symptoms that are assumed to be s ...[more]

PMID: 36309718

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Project description:BackgroundBehçet's syndrome (BS) is an immune-mediated disease characterized by recurrent oral ulcers, genital ulcers, uveitis, and skin symptoms. HLA-B51, as well as other genetic polymorphisms, has been reported to be associated with BS; however, the pathogenesis of BS and its relationship to genetic risk factors still remain unclear. To address these points, we performed immunophenotyping and transcriptome analysis of immune cells from BS patients and healthy donors.MethodsImmuNexUT is a comprehensive database consisting of RNA sequencing data and eQTL database of immune cell subsets from patients with immune-mediated diseases and healthy donors, and flow cytometry data and transcriptome data from 23 BS patients and 28 healthy donors from the ImmuNexUT study were utilized for this study. Differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify genes associated with BS and clinical features of BS. eQTL database was used to assess the relationship between genetic risk factors of BS with those genes.ResultsThe frequency of Th17 cells was increased in BS patients, and transcriptome analysis of Th17 cells suggested the activation of the NFκB pathway in Th17 cells of BS patients. Next, WGCNA was used to group genes into modules with similar expression patterns in each subset. Modules of antigen-presenting cells were associated with BS, and pathway analysis suggested the activation of antigen-presenting cells of BS patients. Further examination of genes in BS-associated modules indicated that the expression of YBX3, a member of a plasmacytoid dendritic cell (pDC) gene module associated with BS, is influenced by a BS risk polymorphism, rs2617170, in pDCs, suggesting that YBX3 may be a key molecule connecting genetic risk factors of BS with disease pathogenesis. Furthermore, pathway analysis of modules associated with HLA-B51 indicated that the association of IL-17-associated pathways in memory CD8+ T cells with HLA-B51; therefore, IL-17-producing CD8+ T cells, Tc17 cells, may play a critical role in BS.ConclusionsVarious cells including CD4+ T cells, CD8+ T cells, and antigen-presenting cells are important in the pathogenesis of BS. Tc17 cells and YBX3 may be potential therapeutic targets in BS.

Dataset Information

Clusters in Behcet's syndrome.

Publications

Clusters in Behçet's syndrome.

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