Mannose binding lectin (MBL) 是一種由肝臟製造的血清蛋白，它具有調理素的功能，並能夠幫助細胞進行吞噬作用，進而刺激補體系統的活化，因此MBL在先天免疫系統中扮演重要角色。過去研究發現，血清中MBL的缺乏與多種疾病的感染風險有關。而MBL缺乏的原因主要來自於MBL-2基因於promoter及 exon 1有基因多型性的發生。這份研究中，我們進行588個台灣地區的中國人及170個結核病病人，分析其MBL-2基因多型性發生的頻率。結果發現一般健康者MBL-2 gene在exon 1，只發生codon 54的變異(A→B)，其頻率為17.9 % (210/1176)。在MBL-2基因promoter -550及 -221 的位置，基因型分佈頻率分別是: HY/HY, 19.2 %; HY/LY, 28.9 %; LY/LY, 16.0 %; HY/LX, 15.1 %；LX/LY, 16.0 %; LX/LX 4.8 %。而在結核病病人與年齡相符合的控制組族群比較發現，結核病病人帶有會製造較高濃度MBL的基因型 (H/H) 頻率明顯比控制組高 (28.2 % vs. 17.3 %, p = 0.018)。我們更進一步利用ex vivo的系統，嘗試釐清MBL在結核病感染中扮演的角色。我們的數據顯示不同MBL 表現型的個體，雖然血清中MBL濃度不同，但影響monocytes吞噬結核菌的百分比，其能力沒有明顯差別。但是血清中存在對熱不穩定的物質，可能影響monocytes吞噬結核菌的結果。另一部分，在過去的研究中，MBL被認為是對抗伺機性感染病原菌Candida albicans (C. albicans) 的第一線防禦。因此，在這份報告中，我們利用ex vivo的系統，探討不同的 MBL-2 基因型對於C. albicans生長及細胞吞噬的影響。我們的數據顯示monocytes及neutrophils吞噬C. albicans的百分比，高 MBL 表現型的個體其能力明顯較低MBL表現型的個體好(24.2 % vs. 11.3 %; p = 0.0004及 9.2 % vs. 3.1 %; p = 0.0157)。而血清抑制C. albicans生長的現象，高 MBL 表現型的個體明顯較低MBL表現型的個體佳 (42 % vs. 18 %; p = 0.0391)。這些發現說明了MBL-2的基因型確實可以預測在互相協調的免疫防禦中，宿主受不同病原菌感染的感受性。這將對未來的個人預防醫學非常有幫助。

Mannose-binding lectin (MBL) is a serum collectin that mediates activation of complement system and is important in innate immunity. Deficiency of MBL is associated with a risk of various infections and arises from structure gene mutation in exon 1 and/or the presence of a low efficiency promoter. In this study, we analyzed the frequencies of haplotypes and genotypes of MBL-2 gene polymorphisms in 588 unrelated Chinese adults and 170 tuberculosis (TB) patients. In Chinese general population, the frequency of the codon 54 mutation of the MBL-2 gene was 17.9 % (210/1176). Additionally, for two polymorphisms at position -550 and -221 in the promoter region, the frequency of several genotypes were: HY/HY, 19.2 %; HY/LY, 28.9 %; LY/LY, 16.0 %; HY/LX, 15.1 %； LX/LY, 16.0 %; LX/LX 4.8 %. Compared with TB patients, we found that main contribution to the significant p value is due to extreme high frequency of genotypes (H/H) that corresponding to high serum MBL in patients with TB versus age-matched control subjects (28.2 % vs. 17.3 %, respectively; p = 0.018). In this study, we try to clarify the role of MBL on TB infection by ex vivo assay. We found that the phagocytosis percentage and mean fluorescence intensity (MFI) of FITC labelled M. tuberculosis in peripheral blood monocytes were not difference between high-MBL phenotypes and low-MBL individuals. However, opsonophagocytosis of M. tuberculosis by monocytes may be influenced by heat labile factors. Some previous in vivo and in vitro studies have demonstrated MBL participated in the first-line defense against Candida albicans (C. albicans), an opportunistic fungal pathogen. However, the influence of individual with various MBL-2 genotypes on yeast phagocytosis and growth are still unknown. We also established an ex vivo system to illustrate the impact of MBL on C. albicans infection. Our data demonstrated that the opsonophagocytosis of monocytes and neutrophils (24.2 % vs. 11.3 %; p = 0.0004, 9.2 % vs. 3.1 %; p = 0.0157, respectively), and C. albicans growth inhibition by plasma from high MBL phenotypes were significantly higher than low MBL phenotypes (42 % vs. 18 %; p = 0.0391). These findings indicate the genotypes of MBL-2 may predict the host infection susceptibility during compromised immune defenses. It is usefully for the predictive and prevention medicine in the future.

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