Duthie Malcolm S, Goto Wakako, Ireton Greg C, Reece Stephen T, Sampaio Lucas H, Grassi A B, Sousa Ana Lucia M, Martelli Celina M T, Stefani Mariane M A, Reed Steven G
Infectious Disease Research Institute, Seattle, WA 98104, USA.
Clin Vaccine Immunol. 2008 Nov;15(11):1659-65. doi: 10.1128/CVI.00234-08. Epub 2008 Sep 10.
The identification of human T-cell antigens of Mycobacterium leprae could improve treatment and help to disrupt the transmission of leprosy by directing diagnosis and vaccine programs. This study screened a panel of M. leprae recombinant proteins for T-cell recall responses, measured by gamma interferon (IFN-gamma) production, among leprosy patients. After initial studies using peripheral blood mononuclear cells from leprosy patients, we transitioned our studies to simple whole-blood assays (WBA), which are more applicable in field or clinical settings. T-cell responses generated in WBA using blood from individuals in Goiânia, Brazil, demonstrated that several M. leprae antigens (ML0276, ML0840, ML1623, ML2044, and 46f) elicited >0.5 IU/ml IFN-gamma, and these proteins were classified as immunogenic and leprosy specific. Several of these individual antigens were recognized by cells from >60% of Brazilian paucibacillary (PB) leprosy patients, and ML0276, ML0840, ML1623, and 46f complemented each other such that 82% of PB patients had strong (>1.25 IU/ml IFN-gamma) responses to at least one of these proteins. These proteins were also recognized by cells from a significant proportion of the household contacts of multibacillary leprosy patients, but in contrast, few responses were observed in active tuberculosis patients or healthy control groups from areas of endemicity. Our results indicate several potential candidate antigens which may be useful for either leprosy diagnosis or vaccination and demonstrate the utility of leprosy WBA that can be applied broadly in clinical or field settings.
鉴定麻风分枝杆菌的人类T细胞抗原可改善治疗,并通过指导诊断和疫苗计划帮助阻断麻风的传播。本研究筛选了一组麻风分枝杆菌重组蛋白,以检测麻风患者中通过γ干扰素(IFN-γ)产生来衡量的T细胞回忆反应。在使用麻风患者外周血单个核细胞进行初步研究后,我们将研究转向更适用于现场或临床环境的简单全血检测(WBA)。使用巴西戈亚尼亚地区个体血液进行的WBA中产生的T细胞反应表明,几种麻风分枝杆菌抗原(ML0276、ML0840、ML1623、ML2044和46f)诱导产生的IFN-γ>0.5 IU/ml,这些蛋白被归类为具有免疫原性且麻风特异性的蛋白。这些单个抗原中的几种被超过60%的巴西少菌型(PB)麻风患者的细胞识别,并且ML0276、ML0840、ML1623和46f相互补充,使得82%的PB患者对这些蛋白中的至少一种有强烈(>1.25 IU/ml IFN-γ)反应。这些蛋白也被多菌型麻风患者的很大一部分家庭接触者的细胞识别,但相比之下,在活动性肺结核患者或来自麻风流行地区的健康对照组中观察到的反应很少。我们的结果表明了几种潜在的候选抗原,它们可能对麻风诊断或疫苗接种有用,并证明了可广泛应用于临床或现场环境的麻风WBA的实用性。