Anti-IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection
Anti-IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection
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DOI：
10.1182/blood-2012-08-452482
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发表时间：
2013-02-21
期刊：
影响因子：
20.3
通讯作者：
Ku, Cheng-Lung
中科院分区：
文献类型：
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作者：
Chi, Chih-Yu;Chu, Chen-Chung;Ku, Cheng-Lung
播散性非结核分支杆菌(DNTM)感染的成人患者通常有严重的免疫系统缺陷。近年来，多项研究表明，抗干扰素-g自身抗体可能在dNTM感染的致病性中起重要作用。在报告的抗干扰素-g自身抗体病例中，有相当一部分显示出自身免疫性疾病的临床或实验室证据。在本研究中，我们确定了19名先前健康的成年人，他们后来患上了dNTM感染，其中17人接受了进一步的免疫学调查。在所有患者的血浆中都发现了能在体外抑制IL-12产生的高效价抗干扰素-g自身抗体。除了dNTM感染，我们的患者中有35%和71%分别患有沙门氏菌病和带状疱疹。这一观察表明，干扰素-g可能在控制沙门氏菌感染和重新激活人类潜伏的水痘-带状疱疹病毒感染方面起关键作用。2等位基因DRB1*16：02 DQB1*05：02(优势比=8.68；95%可信区间3.47~21.90；P=1.1×10(-6)；Pc=3.08×10(-5)，优势比=7.16；95%可信区间3.02~17.05；P=1×10(-7)；Pc=1.4×10(-6))。综上所述，抗干扰素-g自身抗体可能在dNTM感染和潜伏性水痘-带状疱疹病毒感染的再激活中起关键作用，并与人类白细胞抗原-DRB1*16：02和人类白细胞抗原-DQB1*05：02相关。
Adult patients with disseminated nontuberculous mycobacterial (dNTM) infections usually have severe immune system defects. Recently, several studies have shown that anti-IFN-g autoantibodies may play an important role in the pathogenicity of dNTM infections. A considerable proportion of reported cases of anti-IFN-g autoantibodies show either clinical or laboratory evidence of autoimmune disease. In the present study, we identified 19 formerly healthy adults who later developed dNTM infections, of whom 17 were further investigated immunologically. High-titer anti-IFN-g autoantibodies capable of inhibiting IL-12 production in vitro were found in the plasma of all of these patients. In addition to dNTM infection, 35% and 71% of our patients also suffered from salmonellosis and herpes zoster, respectively. This observation suggests that IFN-g may be crucial in controlling salmonella infection and reactivating latent varicella-zoster virus infection in humans. 2 HLA alleles, DRB1*16:02 DQB1*05:02 (odds ratio = 8.68; 95% confidence interval, 3.47-21.90; P = 1.1 x 10(-6); Pc = 3.08 x 10(-5) and odds ratio = 7.16; 95% confidence interval, 3.02-17.05; P = 1 x 10(-7); Pc = 1.4 x 10(-6), respectively), were found in 82% (14 of 17) of our patients. In conclusion, our data suggest that anti-IFN-g autoantibodies may play a critical role in the pathogenesis of dNTM infections and reactivation of latent varicella-zoster virus infection and are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02.