NEJM：研究人员发现导致亚洲人群免疫缺陷的可能原因

在一项于泰国和台湾医院进行研究中，研究人员发现，大多数参与研究的感染人员都会自身产生干扰素-γ（IFN-γ）的抗体，干扰素-γ是一种清除有害感染的重要细胞信号分子。相关研究论文发表在8月23日的国际权威杂志New England Journal of Medicine上。

非结核分枝杆菌是导致肺结核细菌的近亲，其能导致严重的肺部疾病。非结核分枝杆菌（NTM）常见存在于免疫缺陷性疾病患者如艾滋病人中，但非结核分枝杆菌在具备健康免疫系统的人中是罕见的。然而，东南亚地区的研究人员最近报道了几例非结核分枝杆菌感染免疫系统未出现任何问题的人。

这项研究由美国国家过敏和传染病研究所Sarah Browne MD和Peter Burbelo博士领导，共召集203人，年龄在18至78岁之间。在这些参与者中，52例感染非结核分枝杆菌，45例感染其它细菌或并未合并感染非结核分枝杆菌，58例得了肺结核，48名健康志愿者。所有参试者都呈艾滋病毒抗体阴性。

研究者研究参与者的血液样本包括抗体细胞和信号传导分子如IFN-γ等。非结核分枝杆菌（NTM）感染或其它类型感染的人百分之八十八有阻断自身IFN-γ的抗体。

自身抗体抑制IFN-γ的功能，阻碍以清除感染的免疫系统能力，引起一系列综合征使得参与这些研究的参与者更容易受到感染。目前还需要开展更多的工作以明确为什么东南亚人似乎更倾向于罹患这种自身免疫性疾病。因为非结核分枝杆菌（NTM）感染患者或其它类型感染的研究参与者的平均年龄为50岁，研究人员推测，这些抗体由于遗传和环境因素综合的结果会随着时间的发展而变化。既然已经知道了这种综合征的可能原因，研究人员认为靶向产生IFN-γ自身抗体的细胞治疗潜在疾病问题是很有可能的。

与免疫相关的拓展阅读：

• J.Immunol.：自身免疫病相关新药物作用靶点GPCR
• AJRCCM：Th9细胞对肺癌细胞有重要免疫调节作用
• Sci Transl Med：MECP2复制影响免疫系统以及大脑发育
• PLoS ONE：基因组分析证实免疫系统导致自闭症
• JCI：血脑屏障的免疫交换或助力多发性硬化症研究
• Nat Communication：中国科研人员发现胚胎免疫AB面
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Adult-Onset Immunodeficiency in Thailand and Taiwan
Background
Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown.
Methods
We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained.
Results
Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti–interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte–macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering.
Conclusions
Neutralizing anti–interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.)