Adult-onset immunodeficiency in Thailand and Taiwan.
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.).
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. brownesa@niaid.nih.gov
Sarah K
SK
Browne
Peter D
PD
Burbelo
Ploenchan
P
Chetchotisakd
Yupin
Y
Suputtamongkol
Sasisopin
S
Kiertiburanakul
Pamela A
PA
Shaw
Jennifer L
JL
Kirk
Kamonwan
K
Jutivorakool
Rifat
R
Zaman
Li
L
Ding
Amy P
AP
Hsu
Smita Y
SY
Patel
Kenneth N
KN
Olivier
Viraphong
V
Lulitanond
Piroon
P
Mootsikapun
Siriluck
S
Anunnatsiri
Nasikarn
N
Angkasekwinai
Boonmee
B
Sathapatayavongs
Po-Ren
PR
Hsueh
Chi-Chang
CC
Shieh
Margaret R
MR
Brown
Wanna
W
Thongnoppakhun
Reginald
R
Claypool
Elizabeth P
EP
Sampaio
Charin
C
Thepthai
Duangdao
D
Waywa
Camilla
C
Dacombe
Yona
Y
Reizes
Adrian M
AM
Zelazny
Paul
P
Saleeb
Lindsey B
LB
Rosen
Allen
A
Mo
Michael
M
Iadarola
Steven M
SM
Holland
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood*; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009164:Mycobacterium Infections / Q000276:immunology*; D009181:Mycoses / Q000276:immunology; D009894:Opportunistic Infections / Q000276:immunology*; D013624:Taiwan; D013785:Thailand; D014397:Tuberculosis, Pulmonary / Q000276:immunology; D055815:Young Adult
D057134:Antibodies, Neutralizing; D001323:Autoantibodies; C573415:IFNG protein, human; D007371:Interferon-gamma