Association of killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands with susceptibility to Behçet's disease.

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder with remissions and exacerbations. It is thought that defects in the natural killer (NK) cell repertoire may be involved in BD through killer cell immunoglobulin-like receptors (KIRs). This study aimed to evaluate KIR and HLA genes, their interactions in BD patients, and their associations with clinical manifestations. METHOD: The presence or absence of KIR and HLA alleles and genotypes was analysed by polymerase chain reaction sequence-specific primer on genomic DNA of 397 BD patients and 300 healthy controls. RESULTS: None of the KIR genes showed significant effects on BD susceptibility. HLA-C1Asn80 showed a protective effect against BD, whereas HLA-C2Lys80, HLA-B-Bw4Ile80, HLA-B5, and HLA-B51 were associated with a susceptibility risk for BD. In the combination of KIR and HLA genes, the frequencies of HLA genotypes no. 2, 3, 5, and 8, and inhibitory KIR no. 4 were significantly higher in patients than in controls. The frequencies of KIR genotype no. 3 and HLA genotypes no. 1, 4, 6, 7, and 9 were significantly lower in patients than in controls. There were many associations between KIR and HLA genes with clinical features of BD. CONCLUSION: Differences in the frequency of HLA genes, KIR-HLA interactions, and genotypes between BD and healthy controls and their associations with clinical manifestations indicate that NK cells are involved in BD pathogenesis. The observed differences indicated an NK cell activity imbalance in BD patients, and suggest a role of the KIR-HLA repertoire in the development of BD.

Promoter hypermethylation of BCL11B gene correlates with downregulation of gene transcription in ankylosing spondylitis patients.

Methylation of DNA is one of the important regulatory mechanisms of gene transcription. B-cell chronic lymphocytic leukemia/lymphoma 11B (BCL11B) plays a key role in the development, proliferation, differentiation, and survival of T cells. The aim of this study was to evaluate promoter methylation of BCL11B gene and its mRNA level in peripheral blood mononuclear cells (PBMCs) of ankylosing spondylitis (AS) patients in relation to healthy controls and evaluate their correlation with diseases clinical indices. Fifty AS patients and 50 healthy controls entered in this study. PBMCs were isolated from whole blood and RNA and DNA contents of leukocytes were extracted. The expression level of BCL11B gene was measured through real-time PCR assay using SYBR Green Master Mix, and PCR products of bisulfite-treated DNA were sequenced to determine the methylation level of promoter. Decreased transcript and increased promoter methylation levels of BCL11B gene were identified in AS patients compared with healthy controls. Hypermethylation of CpG3 and CpG5 was associated with increased AS risk. Promoter hypermethylation and mRNA overexpression correlated with each other but not with clinical manifestations. We identified aberrancies in expression and methylation of BCL11B gene in AS patients compared with healthy control group; however, they might not impress the clinical face of AS.