Comparative transcriptomic analysis in patients with Behçet syndrome

Behçet syndrome (BS) is a chronic, multisystemic inflammatory condition with unanswered questions regarding its pathogenesis, classification, and rational therapeutics. A microarray-based comparative genome-wide expression analysis was performed to elucidate the molecular mechanisms of BS and identify any potential therapeutic targets. Twenty-nine BS patients (B) and 15 age and sex-matched control subjects (C) were recruited. Patients with BS were grouped as mucocutaneous (M), ocular (O), and vascular (V) according to their clinical phenotypes. GeneChip Human Genome U133 Plus 2.0 arrays were used for gene expression profiling on peripheral blood samples of the patients and the control subjects. Following the documentation of the differentially expressed gene (DEG) sets, the data were further evaluated with bioinformatics analysis/visualization and enrichment tools. Validation of the microarray data were performed using real-time qRT-PCR. When p<0.05 and fold change >2.0 were chosen, the following numbers of DEGs were obtained; B vs. C: 28, M vs. C: 20, O vs. C: 8, V vs. C: 555, M vs. O: 6, M vs. V: 324, O vs. V: 142. Venn diagram analysis indicated only two genes, CLEC12A and IFI27, in the intersection of M vs. C ∩ O vs. C ∩ V vs. C. Another noteworthy gene appeared as CLC in the DEG sets. Cluster analyses successfully clustered distinct clinical phenotypes of BS. While innate immunity-related biological processes were enriched in the M group, adaptive immunity-specific biological processes were significantly enriched in the O and V groups. Distinct clinical phenotypes of BS patients displayed distinct expression profiles. In Turkish patients with BS, expression differences regarding the genes CLEC12A, IFI27, and CLC seemed to be operative in BS pathogenesis. Based on these findings, future research should consider the immunogenetic heterogeneity of BS clinical phenotypes. Two anti-inflammatory genes, namely CLEC12A and CLC, may be valuable as therapeutic targets and may also help design an experimental model in BS. 29 Behçet syndrome patients (B, n=29) and 15 age and sex-matched control subjects (C, n=15) were recruited. Patients with Behçet syndrome were grouped as mucocutaneous (M, n=8), ocular (O, n=5), and vascular (V, n=9) according to their clinical phenotypes. 7 Behçet syndrome patients (D, n=7) were excluded from further analyses, based on their complex clinical phenotypes and significantly low counts. Class comparison analyses were performed among Behçet syndrome subgroups, as well as Behçet syndrome subgroups and the control group.