• Sarah K Browne, Peter D Burbelo, Ploenchan Chetchotisakd, Yupin Suputtamongkol, Sasisopin Kiertiburanakul, Pamela A Shaw, Jennifer L Kirk, Kamonwan Jutivorakool, Rifat Zaman, Li Ding, Amy P Hsu, Smita Y Patel, Kenneth N Olivier, Viraphong Lulitanond, Piroon Mootsikapun, Siriluck Anunnatsiri, Nasikarn Angkasekwinai, Boonmee Sathapatayavongs, Po-Ren Hsueh, Chi-Chang Shieh, Margaret R Brown, Wanna Thongnoppakhun, Reginald Claypool, Elizabeth P Sampaio, Charin Thepthai, Duangdao Waywa, Camilla Dacombe, Yona Reizes, Adrian M Zelazny, Paul Saleeb, Lindsey B Rosen, Allen Mo, Michael Iadarola, and Steven M Holland.
• Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. brownesa@niaid.nih.gov
• N. Engl. J. Med. 2012 Aug 23; 367 (8): 725-34.

BackgroundAutoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown.MethodsWe 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.ResultsPatients 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.ConclusionsNeutralizing 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.).

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