Luz Paola Rosa, Miyazaki Márcia I, Chiminacio Neto Nelson, Padeski Marcela C, Barros Ana Cláudia M, Boldt Angelica B W, Messias-Reason Iara J
Laboratório de Imunopatologia Molecular-Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brasil.
Ambulatório de Atenção ao Paciente Chagásico-Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brasil.
PLoS Negl Trop Dis. 2016 Jan 8;10(1):e0004257. doi: 10.1371/journal.pntd.0004257. eCollection 2016 Jan.
Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy.
恰加斯病（CD）由克氏锥虫引起，其糖部分可被甘露糖结合凝集素（MBL）识别，MBL是一种可激活补体凝集素途径的可溶性模式识别分子。MBL水平和蛋白活性受MBL2基因多态性影响。我们对196例慢性CD患者和202例对照者的MBL2启动子和外显子1进行了测序。导致MBL缺乏的MBL2*C等位基因与预防CD相关（P = 0.007，OR = 0.32）。与对照组相比，患有心脏型疾病的患者中完全不存在携带该等位基因的基因型（P = 0.003）。此外，与具有导致低MBL水平但完全能够激活补体的XA单倍型的心脏病患者相比，具有导致MBL缺乏基因型的心脏病患者心脏损伤较轻（P = 0.003，OR = 0.23）（P = 0.005，OR = 7.07）。在患者中，携带导致MBL缺乏等位基因的患者可能与症状发展相关的细胞因子和趋化因子水平较低（IL9，p = 0.013；PDGFB，p = 0.036；RANTES，p = 0.031）。这些发现表明，遗传决定的MBL缺乏对慢性CD心肌病的发生和发展具有保护作用。
