Browne S.K.Burbelo P.D.Chetchotisakd P.Suputtamongkol Y.Kiertiburanakul S.Shaw P.A.Kirk J.L.Jutivorakool K.Zaman R.Ding L.Hsu A.P.Patel S.Y.Olivier K.N.Lulitanond V.Mootsikapun P.Anunnatsiri S.Angkasekwinai N.Sathapatayavongs B.PO-REN HSUEHShieh C.-C.Brown M.R.Thongnoppakhun W.Claypool R.Sampaio E.P.Thepthai C.Waywa D.Dacombe C.Reizes Y.Zelazny A.M.Saleeb P.Rosen L.B.Mo A.Iadarola M.Holland S.M.2020-12-182020-12-1820120028-4793https://scholars.lib.ntu.edu.tw/handle/123456789/528441BACKGROUND: 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.) Copyright ? 2012 Massachusetts Medical Society.[SDGs]SDG3autoantibody; cytokine antibody; gamma interferon; gamma interferon antibody; granulocyte macrophage colony stimulating factor antibody; neutralizing antibody; adult; adult onset immunodeficiency; aged; antibody detection; antibody titer; article; CD4 lymphocyte count; cell function; cellular immunity; controlled study; cryptococcal meningitis; cytokine production; female; human; human cell; Human immunodeficiency virus infection; humoral immunity; immune deficiency; immunoassay; lung tuberculosis; major clinical study; male; microbial identification; mycobacteriosis; peripheral blood mononuclear cell; plasma; prevalence; priority journal; Taiwan; Thailandjournal article10.1056/NEJMoa11111602-s2.0-84865300679