From Genome-Based In Silico Predictions to Ex Vivo Verification of Leprosy Diagnosis
From Genome-Based In Silico Predictions to Ex Vivo Verification of Leprosy Diagnosis
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DOI：
10.1128/cvi.00414-08
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发表时间：
2009-03-01
影响因子：
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通讯作者：
Dockrell, Hazel M.
中科院分区：
文献类型：
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作者：
Geluk, Annemieke;Spencer, John S.;Dockrell, Hazel M.
每年新发现的数十万麻风病例表明，麻风分枝杆菌感染的传播仍在继续。不幸的是，缺乏识别无症状疾病和/或早期麻风杆菌感染(可能的传播源)的工具。最近对麻风杆菌特有基因的鉴定使得分析人类T细胞对新的麻风杆菌抗原的反应成为可能。在麻风流行的五个不同地区，通过使用麻风患者和对照的外周血单核细胞，测试了具有最有希望的诊断潜力的抗原诱导细胞因子分泌的能力；来自巴西、尼泊尔、孟加拉国、巴基斯坦和埃塞俄比亚的246人被分析了对5种重组蛋白(ML1989、ML1990、ML2283、ML2346和ML2567)和22种合成肽的伽玛干扰素反应。其中，麻风杆菌特有的蛋白ML1989是最常被识别的，而ML2283是麻风杆菌感染/暴露最特异的，因为只有有限数量的结核病患者对这种抗原有反应。然而，在流行地区，所有的蛋白质都被相当数量的对照所识别。T细胞反应与体外对麻风杆菌的反应相关，这表明麻风流行地区的健康对照组暴露于麻风杆菌。重要的是，在流行地区，50%的健康家庭接触者和59%的对照人员没有检测到针对麻风杆菌特异性PGL-I的免疫球蛋白M抗体，但在T细胞检测中对>；=1麻风杆菌蛋白有反应。观察到ML2283和ML0126衍生多肽对麻风患者和健康家庭接触者的特异性T细胞反应，表明麻风支原体多肽具有作为诊断工具的潜力。未来的工作应该集中在开发一种敏感的和现场友好的检测方法，并鉴定能够诱导麻风杆菌特异性T细胞反应的其他多肽和蛋白质。
The detection of hundreds of thousands of new cases of leprosy every year suggests that transmission of Mycobacterium leprae infection still continues. Unfortunately, tools for identification of asymptomatic disease and/or early-stage M. leprae infection (likely sources of transmission) are lacking. The recent identification of M. leprae-unique genes has allowed the analysis of human T-cell responses to novel M. leprae antigens. Antigens with the most-promising diagnostic potential were tested for their ability to induce cytokine secretion by using peripheral blood mononuclear cells from leprosy patients and controls in five different areas where leprosy is endemic; 246 individuals from Brazil, Nepal, Bangladesh, Pakistan, and Ethiopia were analyzed for gamma interferon responses to five recombinant proteins (ML1989, ML1990, ML2283, ML2346, and ML2567) and 22 synthetic peptides. Of these, the M. leprae-unique protein ML1989 was the most frequently recognized and ML2283 the most specific for M. leprae infection/exposure, as only a limited number of tuberculosis patients responded to this antigen. However, all proteins were recognized by a significant number of controls in areas of endemicity. T-cell responses correlated with in vitro response to M. leprae, suggesting that healthy controls in areas where leprosy is endemic are exposed to M. leprae. Importantly, 50% of the healthy household contacts and 59% of the controls in areas of endemicity had no detectable immunoglobulin M antibodies to M. leprae-specific PGL-I but responded in T-cell assays to >= 1 M. leprae protein. T-cell responses specific for leprosy patients and healthy household contacts were observed for ML2283- and ML0126-derived peptides, indicating that M. leprae peptides hold potential as diagnostic tools. Future work should concentrate on the development of a sensitive and field-friendly assay and identification of additional peptides and proteins that can induce M. leprae-specific T-cell responses.