Laboratory of Molecular Immunopathology, Federal University of Paraná, Curitiba, Brazil.
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
Sci Rep. 2018 Jan 11;8(1):526. doi: 10.1038/s41598-017-18937-z.
Complement is an essential element in both innate and acquired immunity contributing to the immunopathogenesis of many disorders, including Chagas Disease (CD). Human complement receptor 1 (CR1) plays a role in the clearance of complement opsonized molecules and may facilitate the entry of pathogens into host cells. Distinct CR1 exon 29 variants have been found associated with CR1 expression levels, increased susceptibility and pathophysiology of several diseases. In this study, CR1 plasma levels were assessed by ELISA and CR1 variants in exon 29 by sequencing in a Brazilian cohort of 232 chronic CD patients and 104 healthy controls. CR1 levels were significantly decreased in CD patients compared to controls (p < 0.0001). The CR1 rs1704660G, rs17047661G and rs6691117G variants were significantly associated with CD and in high linkage disequilibrium. The CR1AGAGTG haplotype was associated with T. cruzi infection (p = 0.035, OR 3.99, CI 1.1-14.15) whereas CR1AGGGTG was related to the risk of chagasic cardiomyopathy (p = 0.028, OR 12.15, CI 1.13-113). This is the first study that provides insights on the role of CR1 in development and clinical presentation of chronic CD.
补体是先天和获得性免疫的重要组成部分，参与许多疾病的免疫发病机制，包括恰加斯病（CD）。人类补体受体 1（CR1）在清除补体调理分子中发挥作用，并可能促进病原体进入宿主细胞。已经发现不同的 CR1 外显子 29 变体与 CR1 表达水平、几种疾病的易感性增加和病理生理学有关。在这项研究中，通过 ELISA 评估 CR1 血浆水平，并通过测序评估外显子 29 中的 CR1 变体，在一个巴西队列的 232 名慢性 CD 患者和 104 名健康对照中进行。与对照组相比，CD 患者的 CR1 水平显著降低（p<0.0001）。CR1 rs1704660G、rs17047661G 和 rs6691117G 变体与 CD 显著相关，并存在高度连锁不平衡。CR1AGAGTG 单倍型与 T. cruzi 感染相关（p=0.035，OR 3.99，CI 1.1-14.15），而 CR1AGGGTG 与恰加斯心肌病的风险相关（p=0.028，OR 12.15，CI 1.13-113）。这是第一项研究，提供了关于 CR1 在慢性 CD 发展和临床表现中的作用的见解。
