Adult-onset immunodeficiency in Thailand and Taiwan.
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Browne Sarah K, Burbelo Peter D, Chetchotisakd Ploenchan, Suputtamongkol Yupin, Kiertiburanakul Sasisopin, Shaw Pamela A, Kirk Jennifer L, Jutivorakool Kamonwan, Zaman Rifat, Ding Li, Hsu Amy P, Patel Smita Y, Olivier Kenneth N, Lulitanond Viraphong, Mootsikapun Piroon, Anunnatsiri Siriluck, Angkasekwinai Nasikarn, Sathapatayavongs Boonmee, Hsueh Po-Ren, Shieh Chi-Chang, Brown Margaret R, Thongnoppakhun Wanna, Claypool Reginald, Sampaio Elizabeth P, Thepthai Charin, Waywa Duangdao, Dacombe Camilla, Reizes Yona, Zelazny Adrian M, Saleeb Paul, Rosen Lindsey B, Mo Allen, Iadarola Michael, Holland Steven M
Аннотация
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.).