Adult-onset immunodeficiency in Thailand and Taiwan.
Adult-onset immunodeficiency in Thailand and Taiwan.
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DOI：
10.1056/nejmoa1111160
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发表时间：
2012-08-23
期刊：
影响因子：
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通讯作者：
Holland SM
中科院分区：
文献类型：
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作者：
Browne SK;Burbelo PD;Chetchotisakd P;Suputtamongkol Y;Kiertiburanakul S;Shaw PA;Kirk JL;Jutivorakool K;Zaman R;Ding L;Hsu AP;Patel SY;Olivier KN;Lulitanond V;Mootsikapun P;Anunnatsiri S;Angkasekwinai N;Sathapatayavongs B;Hsueh PR;Shieh CC;Brown MR;Thongnoppakhun W;Claypool R;Sampaio EP;Thepthai C;Waywa D;Dacombe C;Reizes Y;Zelazny AM;Saleeb P;Rosen LB;Mo A;Iadarola M;Holland SM
抗干扰素γ自身抗体与严重弥散性机会性感染有关，但其重要性和流行程度尚不清楚。我们将来自泰国和台湾的203例患者分为5组：52例弥散性、快速或缓慢生长的非结核分枝杆菌感染患者（1组）；伴有或不伴有非结核分枝杆菌感染的其他机会性感染患者45例（第二组）；播散性肺结核9例（第三组）；肺结核49例（第四组）；健康对照48例（第五组）。记录临床病史，采集血样。1组和2组患者CD4+ t淋巴细胞计数与4组和5组患者相似，且未感染人类免疫缺陷病毒（HIV）。从1组和2组患者中获得的洗涤细胞产生完整的细胞因子，并对细胞因子刺激有反应。相反，从这些患者身上获得的血浆抑制了正常细胞中干扰素γ的活性。1组81%的患者、2组96%的患者、3组11%的患者、4组2%的患者和对照组2%的患者（5组）检测到高滴度抗干扰素-γ自身抗体。检测其他40种抗细胞因子自身抗体。1例隐球菌性脑膜炎患者仅存在针对粒细胞-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遗传缺陷与感染相关。没有家族聚集性。在88%的多次机会性感染的亚洲成年人中检测到中和性抗干扰素-γ自身抗体，并与成人发病免疫缺陷相关，类似于晚期HIV感染。
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 anti-cytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte–macrophage colony-stimulating factor. No other anti-cytokine 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.