KIR/HLA Gene Profile Implication in Systemic Sclerosis Patients from Mexico
KIR/HLA Gene Profile Implication in Systemic Sclerosis Patients from Mexico
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DOI：
10.1155/2019/6808061
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发表时间：
2019-01-01
影响因子：
4.1
通讯作者：
Ernesto Sanchez-Hernandez, Pedro
中科院分区：
文献类型：
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作者：
Carolina Machado-Sulbaran, Andrea;Guadalupe Ramirez-Duenas, Maria;Ernesto Sanchez-Hernandez, Pedro
导论.系统性硬化症（SSc）是一种自身免疫性、炎性和多系统性疾病，其特征在于存在自身抗体和纤维化。发病机制涉及免疫系统细胞如巨噬细胞、NK细胞、T细胞和B细胞之间的相互作用。杀伤细胞免疫球蛋白样受体（KIR）在NK细胞和一些T细胞亚群中表达，其识别HLA I类分子作为配体并参与调节这些细胞的活化和抑制。KIR家族由14个基因和2个假基因组成，根据基因含量，基因型可能为AA和Bx。本研究旨在探讨KIR/HLA基因与SSc基因型及临床特征的关系。方法.我们纳入了50名SSc患者和90名对照受试者（CS）。采用SSP-PCR技术对KIR、HLA-C、-Bw 4、-A03/11进行基因分型。结果在SSc患者中，发现KIR 2DL 2（p=0.0007，p=0.011）、KIR 2DS 4del（p=0.001，p=0.021）和HLA-C2（p=0.02，p=0.09）的频率较高。复合基因型KIR 2DL 2 +/HLA-C1+或KIR 2DL 2 +/HLA-C2+在SSc患者中的频率较高。Bx基因型最常见，与SSc风险相关（p=0.007，OR=3.1，95% CI=1.4-7.9，p=0.014）。在所有个体中均发现iKIR数目高于aKIR（iKIR>aKIR）的基因型; SSc患者中7-8个iKIR基因的基因型增加。我们没有发现KIR基因与临床特征之间的关联。结论结果表明，KIR 2DL 2和2DS 4del可能在SSc的发展中具有风险作用，但与临床表现无关。
Introduction. Systemic Sclerosis (SSc) is an autoimmune, inflammatory, and multisystemic disease characterized by the presence of autoantibodies and fibrosis. The pathogenesis involves the interaction between immune system cells such as macrophages, NK cells, T cells, and B cells. Killer-cell Immunoglobulin-like Receptors (KIR) are expressed in NK cells and some T cell subsets that recognize HLA class I molecules as ligands and are involved in regulating the activation and inhibition of these cells. The KIR family consists of 14 genes and two pseudogenes; according to the gene content, the genotype could be AA and Bx. The aim of this study was to evaluate the association between KIR/HLA genes and genotypes with SSc and the clinical characteristics. Methods. We included 50 SSc patients and 90 Control Subjects (CS). Genotyping of KIR, HLA-C, -Bw4, and -A03/11 was made by SSP-PCR. Results. In SSc patients, a higher frequency of KIR2DL2 (p=0.0007, p=0.011), KIR2DS4del (p=0.001, p=0.021), and HLA-C2 (p=0.02, p=0.09) was found. This is the first study to evaluate the frequency of HLA-A03/11 in SSc patients, of which a low frequency was found in both groups. Compound genotypes KIR2DL2+/HLA-C1+ or KIR2DL2+/HLA-C2+ have a higher frequency in SSc patients. The Bx genotype was the most frequent and was associated with risk to SSc (p=0.007, OR=3.1, 95% CI=1.4-7.9, p=0.014). The genotypes with a higher iKIR number than aKIR (iKIR>aKIR) were found in all individuals; genotypes with 7-8 iKIR genes were increased in SSc patients. We do not find an association between the KIR genes with the clinical characteristics. Conclusion. The results suggest that KIR2DL2 and 2DS4del could have a risk role in the development of SSc, but not with clinical manifestations.