Abstract
Behçet’s disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet’s is “a disease or a syndrome”. To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection “MB vs C” ∩ “OB vs C” ∩ “VB vs C”. Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as “Behçet’s syndrome” (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis.
Highlights
Behçet’s disease (BD) is a multisystemic inflammatory disorder with a strong and complex genetic background [1]
BD patients and control subjects were similar with respect to their ages and gender
By borrowing the expression profiling data of Xavier et al and implementing a “data mining” approach, it was demonstrated that: (1) BD patients demonstrate distinct expression profiles in distinct disease subsets; (2) Different disease associated pathways seem to be functional in different disease expressions of BD; and (3) Four functionally related gene groups, namely, negative regulators of inflammation, neutrophil granule proteins, antigen processing and presentation proteins, and regulators of immune response are differentially expressed in BD patients with respect to healthy controls [8]
Summary
Behçet’s disease (BD) is a multisystemic inflammatory disorder with a strong and complex genetic background [1]. Nearly 80 years after its initial description in 1937, many important questions regarding BD still remain unanswered, in relation to its etiology/pathogenesis and to its classification [2]. Patients with BD display a diverse spectrum of clinical manifestations including ocular, vascular, gastrointestinal, musculoskeletal, and central nervous systems [4]. The presence of well-defined clusters/subsets of BD patients with distinctly associated manifestations of the disease, marked regional variations in the expression of BD around the globe, and the proposal stating that distinct immunological abnormalities are underlying distinct classification groups of BD raised the question whether Behçet’s is “a disease or a syndrome” [4,5,6]. Despite the massive amount of available data, this question is still not answered conclusively
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