International Research in Thailand

我们将212名患者分为五组：包括播散性非结核分枝杆菌病、严重机会性感染、肺结核、播散性结核和正常人。我们在大约90%的严重机会性感染患者中发现了抗干扰素γ自身抗体。所有这些患者均未感染HIV，并且没有其他公认的免疫功能障碍原因。有趣的是，1例隐球菌性脑膜炎患者有抗GM-CSF自身抗体。因此，我们在泰国和中国台湾的一个大型队列中发现，包括非结核分枝杆菌在内的严重机会性感染患者，干扰素γ的自身抗体导致了这种缺陷，并重现了严重的免疫缺陷状态。 作为该项目的结果，为了将这些诊断机会扩展到该领域，我们已经开发了一种简单的抗干扰素γ自身抗体筛选试验，使我们能够识别，跟踪和滴定活性。 认识到抗干扰素γ自身抗体是严重机会性感染的原因，导致使用利妥昔单抗控制其抗体，从而控制其感染。 我们现在正在研究这些自身抗体识别的表位。我们也开始寻找隐球菌病的自身抗体。

We enrolled 212 patients into five groups: including those with disseminated nontuberculous mycobacterial disease, severe opportunistic infections, pulmonary tuberculosis, disseminated tuberculosis, and normals. We identified anti-interferon gamma autoantibodies 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, one patient with cryptococcal meningitis had anti-GM-CSF autoantibodies. 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. The recognition of anti-interferon gamma autoantibodies as the cause of severe opportunistic infections has led to the use of rituximab for control of their antibodies and therefore their infections. We are now engaged in characterizing the epitope or epitopes that are being recognized by these autoantibodies. We have also begun a search for autoantibodies in cryptococcosis, as well.