International Research in Thailand

在过去的一年里，我们对新入学进行了开放、注册和关闭，因为我们在6个月内达到了总入学目标。我们将212例患者分为五组，包括严重机会性感染患者、肺结核患者、弥散性肺结核患者和正常人。我们对这些患者的血浆进行了深入分析，寻找41种不同细胞因子的自身抗体。唯一与机会性感染相关的抗细胞因子自身抗体是抗干扰素γ自身抗体，在大约90%的严重机会性感染患者中发现。所有这些患者均未感染艾滋病毒，也没有其他已知的免疫功能障碍原因。有趣的是，肺结核患者和弥散性肺结核患者的抗干扰素γ自身抗体水平不显著。这些结果具有高度统计学意义。重要的是，机会性感染患者的全部缺陷似乎都在血浆成分上，因为当这些患者的细胞被洗净了自己的血浆后，它们的功能就恢复正常了。此外，将抑制血浆添加到正常细胞中，在体外完全再现了缺陷。因此，我们在泰国和台湾的大量患者中发现，严重的机会性感染，包括非结核分枝杆菌，干扰素γ的自身抗体是导致缺陷和再现严重免疫缺陷状态的原因。

This past year we have opened, enrolled, and closed our study to new enrollment because we reached our total enrollment target in 6 months. We enrolled 212 patients into five groups, including those with severe opportunistic infections, patients with pulmonary tuberculosis, patients with disseminated tuberculosis, and normals. We have performed in-depth analysis of the plasma from these patients looking for autoantibodies to 41 different cytokines. The only anticytokine autoantibody that was associated with opportunistic infection was the anti-interferon gamma autoantibody, which was found in approximately 90% of those with severe opportunistic infections. All these patients were HIV uninfected and had no other recognized cause of immune dysfunction. Interestingly, those with pulmonary tuberculosis and those with disseminated tuberculosis did not have significant levels of anti-interferon gamma autoantibodies. These results were highly statistically significant. Importantly, the entire defect in those with opportunistic infections seems to be in the plasma component, since when those patients cells were washed clean of their own plasma, their function as normal. Further, addition of inhibitory plasma to normal cells fully recapitulated the defect in vitro. Therefore, we have shown in a large cohort of patients in Thailand and Taiwan with severe opportunistic infections, including nontuberculous mycobacteria, that autoantibodies to interferon gamma account for the defect and reproduce a state of severe immunodeficiency. As a result of this project and in order to extend these diagnostic opportunities to the field, we have developed a simple screening assay for anti-interferon gamma autoantibodies that will allow us to identify, follow, and titer activity.