Ayo Christiane Maria, Reis Pâmela Guimarães, Dalalio Márcia Machado de Oliveira, Visentainer Jeane Eliete Laguila, Oliveira Camila de Freitas, de Araújo Silvana Marques, de Oliveira Marques Divina Seila, Sell Ana Maria
Post Graduation Program of Biosciences Applied to Pharmacy, Department of Analysis Clinical and Biomedicine, Maringa State University, Maringa, Parana, Brazil.
Basic Health Sciences, Maringa State University, Maringa, Parana, Brazil.
PLoS Negl Trop Dis. 2015 May 15;9(5):e0003753. doi: 10.1371/journal.pntd.0003753. eCollection 2015 May.
The aim of this study was to investigate the influence of killer cell immunoglobulin-like receptor (KIR) genes and their human leucocyte antigen (HLA) ligands in the susceptibility of chronic Chagas disease. This case-control study enrolled 131 serologically-diagnosed Chagas disease patients (59 men and 72 women, mean age of 60.4 ± 9.8 years) treated at the University Hospital of Londrina and the Chagas Disease Laboratory of the State University of Maringa. A control group was formed of 165 healthy individuals - spouses of patients or blood donors from the Regional Blood Bank in Maringa (84 men and 81 women, with a mean age of 59.0 ± 11.4 years). Genotyping of HLA and KIR was performed by PCR-SSOP. KIR2DS2-C1 in the absence of KIR2DL2 (KIR2DS2+/2DL2-/C1+) was more frequent in Chagas patients (P = 0.020; Pc = 0.040; OR = 2.14) and, in particular, those who manifested chronic chagasic cardiopathy-CCC (P = 0.0002; Pc = 0.0004; OR = 6.64; 95% CI = 2.30-18.60) when compared to the control group, and when CCC group was compared to the patients without heart involvement (P = 0.010; Pc = 0.020; OR = 3.97). The combination pair KIR2DS2+/2DL2-/KIR2DL3+/C1+ was also positively associated with chronic chagasic cardiopathy. KIR2DL2 and KIR2DS2 were related to immunopathogenesis in Chagas disease. The combination of KIR2DS2 activating receptor with C1 ligand, in the absence of KIR2DL2, may be related to a risk factor in the chronic Chagas disease and chronic chagasic cardiopathy.
本研究旨在探讨杀伤细胞免疫球蛋白样受体(KIR)基因及其人类白细胞抗原(HLA)配体对慢性恰加斯病易感性的影响。这项病例对照研究纳入了131例经血清学诊断的恰加斯病患者(59名男性和72名女性,平均年龄60.4±9.8岁),他们在隆德里纳大学医院和马林加州立大学恰加斯病实验室接受治疗。对照组由165名健康个体组成,他们是患者的配偶或马林加地区血库的献血者(84名男性和81名女性,平均年龄59.0±11.4岁)。通过聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)对HLA和KIR进行基因分型。与对照组相比,在缺乏KIR2DL2(KIR2DS2+/2DL2-/C1+)的情况下,KIR2DS2-C1在恰加斯病患者中更为常见(P = 0.020;校正P值Pc = 0.040;比值比OR = 2.14),尤其是那些表现为慢性恰加斯性心脏病(CCC)的患者(P = 0.0002;Pc = 0.0004;OR = 6.64;95%可信区间CI = 2.30 - 18.60),并且当CCC组与无心脏受累的患者相比时(P = 0.010;Pc = 0.020;OR = 3.97)。组合对KIR2DS2+/2DL2-/KIR2DL3+/C1+也与慢性恰加斯性心脏病呈正相关。KIR2DL2和KIR2DS2与恰加斯病的免疫发病机制有关。在缺乏KIR2DL2的情况下,KIR2DS2激活受体与C1配体的组合可能与慢性恰加斯病和慢性恰加斯性心脏病的危险因素有关。