Behçet’s disease and genes within the major histocompatibility complex region

Abstract

The role of genetic background in the development of Behçet's disease (BD) is best reflected by the strong association between HLA-B*51 and BD that has been demonstrated across various ethnic groups. The contributions made by other HLA or non-HLA genes to disease susceptibility have been suggested by the results of a number of gene association studies, although the true associations between the genes located within the major histocompatibility complex (MHC) region and BD have often been doubted due to the possibility of linkage disequilibrium of those genes with HLA-B*51. The presence of a true susceptibility gene in the vicinity of HLA-B*51 has also been extensively investigated because of the limited evidence that directly relates HLA-B*51 to the pathogenesis of BD. However, recent genome-wide association studies have confirmed that HLA-B*51 is primarily associated with BD and that there are multiple susceptibility loci other than HLA-B*51. In this review, we discuss BD-associated genes within the MHC region and their biological roles in the pathogenesis of BD.

Successful mesenchymal stem cell treatment of leg ulcers complicated by Behcet disease

“…To date, available evidence has suggested that tumor necrosis factor (TNF) inhibitors may be effective for treatment of leg ulcers. [ 5 , 6 ] Mesenchymal stem cells (MSCs), mainly isolated from bone marrow and some other sources such as umbilical cord blood, possess unlimited self-renewal and pluripotential capacity. [ 7 ] Several studies have documented the immunosuppressive and anti-inflammatory effect that MSC may exhibit in different diseases.…”

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“…The identification of the gene in this novel susceptibility locus may make a great contribution to more understanding of the pathogenesis of BD, as it may explain the expression of the disease in HLA-B*51 negative individuals, and also the fact that not all HLA-B*51 positive individuals develop the disease. It is likely that the expression of genes other than HLA-B*51, serves as an additional risk factor of developing BD [13].…”

“…In humans, a significant correlation was observed between neutrophil hyper function and HLA-B*51 positivity, regardless of the presence of BD. Thus, it appears that HLA-B*51 might be responsible, at least in part, for neutrophil hyperactivity in BD, and the possession of HLA-B*51 is not sufficient to induce clinical disease, and additional genetic or environmental factors are required to trigger disease development [13].…”

“…Non-HLA genes within the MHC region: Although a strong association between BD and HLA-B*51 has long been known, a putative susceptibility gene near HLA-B*51 was extensively sought because of limited evidence of a direct relation between HLA-B*51 and the pathogenesis of BD. In this respect, tumor necrosis factor (TNF) and MICA have been investigated as strong candidate genes [13]. Factor) gene: TNF is a multifunctional cytokine plays a central role in the initiation and regulation of the immune response.…”

Inflammation-related cytokine gene polymorphisms in Behçet’s disease

“… 40 Besides HLA-B51 molecules, SNPs in TNF and IL-10 genes have been implicated in susceptibility to BD. 24 , 41 – 43 However, the results are inconsistent and variations are found among several ethnic populations. So in this study, the association of five polymorphisms in TNF-α , - β , and IL-10 genes with BD susceptibility risk in Saudi patients was evaluated.…”