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肾移植中杀伤细胞免疫球蛋白样受体-人类白细胞抗原配体不相容性的影响

Impact of killer immunoglobulin-like receptor-human leukocyte antigens ligand incompatibility among renal transplantation.

作者信息

Alam S, Rangaswamy D, Prakash S, Sharma R K, Khan M I, Sonawane A, Agrawal S

机构信息

Department of Biosciences, Integral University, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India ; Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

出版信息

Indian J Nephrol. 2015 Jan-Feb;25(1):27-33. doi: 10.4103/0971-4065.134655.

Abstract

Killer immunoglobulin-like receptor (KIR) gene shows a high degree of polymorphism. Natural killer cell receptor gets activated once they bind to self-human leukocyte antigens (HLAs) with specific ligand. KIR gene and HLA ligand incompatibility due to the presence/absence of KIR in the recipient and the corresponding HLA ligand in the allograft may impact graft survival in solid organ transplantation. This study evaluates the effect of matches between KIR genes and known HLA ligands. KIR genotypes were determined using sequence specific primer polymerase chain reaction. Presence of certain KIR in a recipient, where the donor lacked the corresponding HLA ligand was considered a mismatch. The allograft was considered matched when both KIR receptor and HLA alloantigen reveald compatibility among recipient and donor. The data revealed better survival among individuals with matched inhibitory KIR receptors and their corresponding HLA ligands (KIR2DL2/DL3-HLAC2, KIR3DL1-HLABw4). On the contrary, no adverse effect was seen for matched activating KIR receptors and their corresponding HLA ligands. One of the activating gene KIR2DS4 showed risk (P = 0.0413, odds ratio = 1.91, 95% confidence interval = 1.02-3.57) association with renal allograft rejection. We conclude that the presence of inhibitory KIR gene leads to better survival; whereas activating motifs show no significant role in renal allograft survival.

摘要

杀伤细胞免疫球蛋白样受体(KIR)基因表现出高度的多态性。自然杀伤细胞受体一旦与具有特定配体的自身人类白细胞抗原(HLA)结合就会被激活。由于受者体内KIR的存在与否以及同种异体移植物中相应HLA配体的存在与否导致的KIR基因与HLA配体不相容,可能会影响实体器官移植中的移植物存活。本研究评估了KIR基因与已知HLA配体之间匹配的影响。使用序列特异性引物聚合酶链反应确定KIR基因型。如果受者体内存在某种KIR而供者缺乏相应的HLA配体,则认为是错配。当KIR受体和HLA同种异体抗原在受者和供者之间显示出相容性时,同种异体移植物被认为是匹配的。数据显示,抑制性KIR受体与其相应HLA配体匹配的个体(KIR2DL2/DL3-HLAC2、KIR3DL1-HLABw4)的存活率更高。相反,匹配的激活性KIR受体及其相应HLA配体未观察到不良影响。其中一个激活性基因KIR2DS4显示出与肾移植排斥反应的风险关联(P = 0.0413,优势比 = 1.91,95%置信区间 = 1.02 - 3.57)。我们得出结论,抑制性KIR基因的存在导致更好的存活率;而激活性基序在肾移植存活中未显示出显著作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68db/4323909/cd8ba227678e/IJN-25-27-g004.jpg

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