Cervera Carlos, Lozano Francisco, Saval Nuria, Gimferrer Idoia, Ibañez Ana, Suárez Belen, Linares Laura, Cofán Federico, Ricart Maria Jose, Esforzado Nuria, Marcos María Angeles, Pumarola Tomás, Oppenheimer Federico, Campistol Josep M, Moreno Asunción
Department of Infectious Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine, University of Barcelona, Barcelona, Spain.
Transplantation. 2007 Jun 15;83(11):1493-500. doi: 10.1097/01.tp.0000264999.71318.2b.
Genetically defined deficiencies in key components of the innate immune system have been associated with a greater risk of infection. The aim of this study was to assess the influence of genetic variability of innate immune receptors (mannose-binding lectin [MBL], mannose-associated serine-protease-2 [MASP-2], and Toll-like receptors [TLR4]) in the risk of infections after a kidney transplantation.
All patients undergoing a kidney or kidney-pancreas transplantation during a 3-year period were included. Functionally relevant mutations in MBL2, MASP2, and TLR4 genes were determined by DNA sequencing. The incidence of major bacterial infections, asymptomatic cytomegalovirus (CMV) infection, and CMV disease were compared among groups.
There were no differences regarding major transplant characteristics among groups. Older age, requirements for posttransplant hemodialysis, and pretransplant diabetes, but not gene polymorphisms, were associated with a greater number of bacterial infections. In univariate analysis, low-MBL genotypes were associated with CMV disease in pretransplant CMV seropositive patients (P=0.015), whereas the TLR4 mutation was associated with higher risk of CMV primary infection (P=0.024). TLR4 mutation was an independent factor associated with CMV disease (odds ratio 5.84, 95% confidence interval 1.35-25.20, P=0.018).
Polymorphisms of innate immunity receptors, especially TLR4 mutation, were associated with higher risk of CMV disease, while susceptibility to other infectious disorders was not observed.
先天性免疫系统关键成分的基因缺陷与感染风险增加有关。本研究的目的是评估先天性免疫受体(甘露糖结合凝集素[MBL]、甘露糖相关丝氨酸蛋白酶-2[MASP-2]和Toll样受体[TLR4])的基因变异对肾移植后感染风险的影响。
纳入3年内接受肾或肾胰联合移植的所有患者。通过DNA测序确定MBL2、MASP2和TLR4基因的功能相关突变。比较各组中主要细菌感染、无症状巨细胞病毒(CMV)感染和CMV疾病的发生率。
各组间主要移植特征无差异。年龄较大、移植后需要血液透析以及移植前患有糖尿病,但不是基因多态性,与更多的细菌感染有关。在单因素分析中,低MBL基因型与移植前CMV血清学阳性患者的CMV疾病相关(P=0.015),而TLR4突变与CMV原发感染的较高风险相关(P=0.024)。TLR4突变是与CMV疾病相关的独立因素(比值比5.84,95%置信区间1.35-25.20,P=0.018)。
先天性免疫受体的多态性,尤其是TLR4突变,与CMV疾病的较高风险相关,而未观察到对其他感染性疾病的易感性。