Behçet syndrome: The disturbed balance between anti- (CLEC12A, CLC) and
pro-inflammatory (IFI27) gene expressions
Abstract
Behçet syndrome (BS) is a chronic, multisystemic inflammatory condition
with unanswered questions regarding its pathogenesis and rational
therapeutics. A microarray-based comparative transcriptomic 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 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 expression profiling on peripheral blood samples of the
patients and the control subjects. Following 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 was performed using 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 and O
vs. C and 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 processes were enriched
in the M group, adaptive immunity-specific processes were significantly
enriched in the O and V groups. Distinct clinical phenotypes of BS
patients displayed distinct expression profiles. In Turkish BS patients,
expression differences regarding the genes CLEC12A, IFI27, and CLC
seemed to be operative in the disease 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.