Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil.
BMC Infect Dis. 2011 Jan 26;11:26. doi: 10.1186/1471-2334-11-26.
Leprosy is a chronic infectious disease caused by Mycobacterium leprae that can manifest a wide variety of immunological and clinical outcomes ranging from potent humoral responses among borderline lepromatous (BL) and lepromatous (LL) patients to strong cellular responses among tuberculoid (TT) and borderline tuberculoid (BT) patients. Until recently, relatively little has been known about the immune responses to individual proteins of M. leprae recognized during leprosy.
The immune reactivity to a panel of 33 M. leprae recombinant proteins was evaluated among leprosy patients and controls from a high endemic area for leprosy (Goiania/GO, Central Brazil). Serum IgG responses were measured by ELISA (45 participants/group) and T cell responses (20 participants/group) were evaluated by IFN-gamma production in 24 hours whole blood cultures with antigen (whole blood assay-WBA). Study groups were newly diagnosed, untreated TT/BT and BL/LL leprosy patients classified by Ridley Jopling criteria and household contacts of BL/LL patients (HHC). Control groups were HIV-1 negative pulmonary tuberculosis patients (TB) and healthy individuals from the same endemic area (EC). In silico predictions indicated the level of identity of M. leprae proteins with homologues in other mycobacteria and the presence of T cell and B cell epitopes.
Despite the prediction that all proteins would be reactive, 16 of 33 (48%) of the single proteins tested were immunogenic (recognized in WBA or ELISA) and seventeen were non-immunogenic (not recognized in either assay). Among the 16 immunogenic proteins, 9 were considered leprosy specific in WBA inducing cell-mediated IFN-gamma secretion from TT/BT patients and HHC. Three of these proteins were also leprosy specific in serology being recognized by serum IgG from LL/BL patients. Seven of the immunogenic proteins were not leprosy specific.
New M. leprae antigens recognized by antibody responses of BL/LL patients and cellular responses of TT/BT leprosy patients were identified. An improved serological diagnostic test for leprosy could be developed by incorporating these IgG-reactive antigens to the current PGL-I based tests. Moreover our data indicate that the WBA is a robust, relatively simple and user friendly format for a T cell based diagnostic test. The field use of these test formats in leprosy endemic countries could contribute to early leprosy diagnosis before the development of deformities and disabilities.
麻风病是一种由麻风分枝杆菌引起的慢性传染病，可表现出广泛的免疫和临床结果，从边界偏瘤型（BL）和瘤型（LL）患者中强有力的体液反应到结核样型（TT）和边界结核样型（BT）患者中强烈的细胞反应不等。直到最近，人们对麻风分枝杆菌在麻风病中识别的单个蛋白的免疫反应还知之甚少。
在巴西中部高麻风流行地区（戈亚尼亚/GO），评估了麻风病患者和对照组中一组 33 种麻风分枝杆菌重组蛋白的免疫反应。通过 ELISA（每组 45 名参与者）测量血清 IgG 反应，并用抗原（全血测定-WBA）在 24 小时全血培养中评估 IFN-γ产生的 T 细胞反应（每组 20 名参与者）。研究组为新诊断、未经治疗的 TT/BT 和 BL/LL 麻风病患者，按 Ridley Jopling 标准分类，以及 BL/LL 患者的家庭接触者（HHC）。对照组为 HIV-1 阴性肺结核患者（TB）和来自同一流行地区（EC）的健康个体。基于计算机的预测表明，麻风分枝杆菌蛋白与其他分枝杆菌同源物的同源性水平以及 T 细胞和 B 细胞表位的存在。
尽管预测所有蛋白质都会产生反应，但在测试的 33 种单一蛋白质中，有 16 种（48%）具有免疫原性（在 WBA 或 ELISA 中被识别），17 种没有免疫原性（在两种测定中均未被识别）。在 16 种免疫原性蛋白质中，有 9 种被认为在 WBA 中具有麻风特异性，能诱导 TT/BT 患者和 HHC 的细胞介导 IFN-γ分泌。其中 3 种在血清学上也具有麻风特异性，能被 LL/BL 患者的血清 IgG 识别。有 7 种免疫原性蛋白不是麻风特异性的。
鉴定出了 BL/LL 患者的抗体反应和 TT/BT 麻风病患者的细胞反应识别的新麻风分枝杆菌抗原。通过将这些 IgG 反应性抗原纳入当前基于 PGL-I 的检测，可以开发出更灵敏的麻风病血清学诊断检测。此外，我们的数据表明，WBA 是一种强大、相对简单和用户友好的 T 细胞诊断检测格式。在麻风流行国家中使用这些检测格式，可以在出现畸形和残疾之前，有助于早期诊断麻风病。
