Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
N Engl J Med. 2012 Aug 23;367(8):725-34. doi: 10.1056/NEJMoa1111160.
Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown.
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.
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.
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.).
针对干扰素-γ 的自身抗体与严重播散性机会性感染有关，但它们的重要性和流行率尚不清楚。
我们从泰国和中国台湾的五个地点招募了 203 名人员，分为五组：52 名患有播散性、快速或缓慢生长的非结核分枝杆菌感染的患者（第 1 组）；45 名患有另一种机会性感染的患者，包括或不包括非结核分枝杆菌感染（第 2 组）；9 名患有播散性肺结核的患者（第 3 组）；49 名患有肺结核的患者（第 4 组）；以及 48 名健康对照者（第 5 组）。记录临床病史，并采集血液标本。
第 1 组和第 2 组患者的 CD4+T 淋巴细胞计数与第 4 组和第 5 组患者相似，并且他们未感染人类免疫缺陷病毒（HIV）。从第 1 组和第 2 组患者中获得的洗涤细胞具有完整的细胞因子产生和对细胞因子刺激的反应。相比之下，来自这些患者的血浆抑制了正常细胞中干扰素-γ 的活性。在第 1 组患者中有 81%，在第 2 组患者中有 96%，在第 3 组患者中有 11%，在第 4 组患者中有 2%，在第 5 组对照者中有 2%的患者检测到高滴度的抗干扰素-γ 自身抗体。还检测了 40 种其他抗细胞因子自身抗体。一名患有隐球菌性脑膜炎的患者仅具有针对粒细胞-巨噬细胞集落刺激因子的自身抗体。没有其他抗细胞因子自身抗体或与感染相关的遗传缺陷。没有家族聚集性。
在患有多种机会性感染的亚洲成年人中检测到中和抗干扰素-γ 自身抗体，与类似于晚期 HIV 感染的成人发病免疫缺陷相关。（由国家过敏和传染病研究所和国家牙科和颅面研究所资助；临床试验.gov 编号，NCT00814827）。
