Messias-Reason I J, Schafranski M D, Kremsner P G, Kun J F J
Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, 72074 Tübingen, Germany.
Clin Exp Immunol. 2009 Sep;157(3):395-9. doi: 10.1111/j.1365-2249.2009.03975.x.
Ficolins are pattern-recognition proteins involved in innate immunity, which upon binding to their specific pathogen-associated molecular patterns on the microbial surfaces trigger the immune response either by binding to collectin cellular receptors or by initiating the complement lectin pathway. In humans, three ficolin genes have been identified, which encode ficolin-1 (M-ficolin), ficolin-2 (L-ficolin) and ficolin-3 (H-ficolin or Hakata antigen). Ficolin-2 was shown to bind to lipoteichoic acid, a cell wall constituent in all Gram-positive bacteria such as Streptococcus pyogenes, which is the aetiological agent of rheumatic fever (RF) and its most severe sequelae, chronic rheumatic heart disease (CRHD). Here we investigated polymorphisms in the promoter region of the FCN2 gene (at positions -986/-602 and +4) in 122 patients with RF and CRHD and in 210 healthy subjects from the same geographic region and socioeconomic background. The haplotype -986/-602/-4 G/G/A, which is related to low levels of L-ficolin, was observed more frequently in the CRHD group when compared to the healthy subjects [99/162, 61.1% versus 211/420, 50.2%, odds ratio (OR) 1.6, confidence interval (CI) 95% 1.1-2.3, P = 0.021]. The haplotype -986/-602/-4 A/G/A was observed more frequently in the healthy group when compared to the affected (RF plus CRHD) subjects (31/420, 7.4% versus 6/244, 2.5%, OR 3.2, CI 95% 0.13-0.77, P = 0.008). Based on those findings, one can conclude that polymorphisms associated with low levels of L-ficolin level may predispose an individual to recurrent and/or more severe streptococcal infection.
纤维胶凝蛋白是参与固有免疫的模式识别蛋白，其与微生物表面特定的病原体相关分子模式结合后，通过与凝集素细胞受体结合或启动补体凝集素途径来触发免疫反应。在人类中，已鉴定出三个纤维胶凝蛋白基因，它们分别编码纤维胶凝蛋白-1（M-纤维胶凝蛋白）、纤维胶凝蛋白-2（L-纤维胶凝蛋白）和纤维胶凝蛋白-3（H-纤维胶凝蛋白或博多抗原）。已证明纤维胶凝蛋白-2能与脂磷壁酸结合，脂磷壁酸是所有革兰氏阳性菌（如化脓性链球菌）细胞壁的组成成分，化脓性链球菌是风湿热（RF）及其最严重后遗症——慢性风湿性心脏病（CRHD）的病原体。在此，我们研究了122例RF和CRHD患者以及来自同一地理区域和社会经济背景的210名健康受试者中FCN2基因启动子区域（-986/-602和+4位置）的多态性。与健康受试者相比，CRHD组中与低水平L-纤维胶凝蛋白相关的单倍型-986/-602/-4 G/G/A出现的频率更高[99/162，61.1%对211/420，50.2%，优势比（OR）1.6，95%置信区间（CI）1.1 - 2.3，P = 0.021]。与患病（RF加CRHD）受试者相比，健康组中-986/-602/-4 A/G/A单倍型出现的频率更高（31/420，7.4%对6/244，2.5%，OR 3.2，CI 95% 0.13 - 0.77，P = 0.008）。基于这些发现，可以得出结论，与低水平L-纤维胶凝蛋白相关的多态性可能使个体易患复发性和/或更严重的链球菌感染。
