Gamma interferon responses induced by a panel of recombinant and purified mycobacterial antigens in healthy, non-Mycobacterium bovis BCG-vaccinated Malawian young adults

Gamma interferon responses induced by a panel of recombinant and purified mycobacterial antigens in healthy, non-Mycobacterium bovis BCG-vaccinated Malawian young adults
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DOI:
10.1128/cdli.10.4.602-611.2003
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发表时间:
2003-07-01
期刊:
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子:
--
通讯作者:
Dockrel, HM
Dockrel, HM
中科院分区:
其他
文献类型:
--
作者:
Black, GF;Weir, RE;Dockrel, HM

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我们以前已经表明,年轻的成年人生活在农村地区的北方马拉维表现出更大的γ干扰素(IFN-γ)的反应,纯化的蛋白衍生物(PPD)从环境分枝杆菌比PPD结核分枝杆菌。为了确定生活在非洲农村人群中的个体暴露和致敏的分枝杆菌物种,我们测试了T细胞对来自分枝杆菌的重组和纯化抗原的识别。结核分枝杆菌(38 kDa,MPT 64,ESAT-6)、M. bovis(MPB70),M. bovis BCG(Ag 85)和M.麻风(65 kDa,35 kDa和18 kDa),在>600个非M。在马拉维北方的卡隆加区,通过酶联免疫吸附试验(ELISA)在稀释的全血培养物的第6天上清液中测量IFN-γ。重组M.麻风菌35-kDa和18-kDa和纯化的天然M.牛BCG Ag 85抗原诱导了最高百分比的应答者,尽管麻风病和牛结核病现在在该人群中很少见。分枝结核抗原ESAT-6和MPT 64;牛抗原MPB 70诱导的应答者百分比最低。其中一名受试者随后发展为肺外结核;该个体对Mantoux试验有15 mm直径的反应,并对M.结核PPD、Ag 85、MPT 64和ESAT-6,但不与任何麻风抗原结合。我们的结论是,在这个农村非洲人口,暴露于M。结核或M.牛分枝杆菌感染的频率远低于暴露于环境分枝杆菌如M. avium,其抗原与M.麻风35 kDa和18 kDa抗原。M.结核病ESAT-6显示出与Mantoux皮肤测试硬结大小的最强相关性,这表明在三种M.结核抗原检测提供了暴露于或感染M的最佳指示。结核
We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-gamma) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD from Mycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified antigens from M. tuberculosis (38 kDa, MPT64, and ESAT-6), M. bovis (MPB70), M. bovis BCG (Ag85), and M. leprae (65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovis BCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-gamma was measured by enzyme-linked immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinant M. leprae 35-kDa and 18-kDa and purified native M. bovis BCG Ag85 antigens induced the highest percentages of responders, though both leprosy and bovine tuberculosis are now rare in this population. The M. tuberculosis antigens ESAT-6 and MPT64 and the M. bovis antigen MPB70 induced the lowest percentages of responders. One of the subjects subsequently developed extrapulmonary tuberculosis; this individual had a 15-mm-diameter reaction to the Mantoux test and responded to M. tuberculosis PPD, Ag85, MPT64, and ESAT-6 but not to any of the leprosy antigens. We conclude that in this rural African population, exposure to M. tuberculosis or M. bovis is much less frequent than exposure to environmental mycobacteria such as M. avium, which have antigens homologous to the M. leprae 35-kDa and 18-kDa antigens. M. tuberculosis ESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the three M. tuberculosis antigens tested it provided the best indication of exposure to, or infection with, M. tuberculosis.