TY - JOUR
T1 - Adult-onset immunodeficiency in Thailand and Taiwan
AU - Browne, Sarah K.
AU - Burbelo, Peter D.
AU - Chetchotisakd, Ploenchan
AU - Suputtamongkol, Yupin
AU - Kiertiburanakul, Sasisopin
AU - Shaw, Pamela A.
AU - Kirk, Jennifer L.
AU - Jutivorakool, Kamonwan
AU - Zaman, Rifat
AU - Ding, Li
AU - Hsu, Amy P.
AU - Patel, Smita Y.
AU - Olivier, Kenneth N.
AU - Lulitanond, Viraphong
AU - Mootsikapun, Piroon
AU - Anunnatsiri, Siriluck
AU - Angkasekwinai, Nasikarn
AU - Sathapatayavongs, Boonmee
AU - Hsueh, Po Ren
AU - Shieh, Chi Chang
AU - Brown, Margaret R.
AU - Thongnoppakhun, Wanna
AU - Claypool, Reginald
AU - Sampaio, Elizabeth P.
AU - Thepthai, Charin
AU - Waywa, Duangdao
AU - Dacombe, Camilla
AU - Reizes, Yona
AU - Zelazny, Adrian M.
AU - Saleeb, Paul
AU - Rosen, Lindsey B.
AU - Mo, Allen
AU - Iadarola, Michael
AU - Holland, Steven M.
PY - 2012/8/23
Y1 - 2012/8/23
N2 - BACKGROUND: 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.)
AB - BACKGROUND: 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.)
UR - http://www.scopus.com/inward/record.url?scp=84865300679&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1111160
DO - 10.1056/NEJMoa1111160
M3 - Article
AN - SCOPUS:84865300679
SN - 0028-4793
VL - 367
SP - 725
EP - 734
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 8
ER -