Adult patients with disseminated nontuberculous mycobacterial (dNTM) infections usually have severe immune system defects, such as AIDS or autoimmune diseases. Recently, several reports have shown that anti-IFN-γ autoantibodies may play an important role in the pathogenicity of dNTM infections. However, a considerable proportion of reported anti-IFN-γ autoantibodies cases either have clinical or laboratory evidence of autoimmune disease. In this study, we identified 19 previously healthy adults who suffered from dNTM infections, and 17 received further immunological function assays. High-titer anti-IFN-γ autoantibodies with activity inhibiting IL-12 production were found in the plasma of all of the patients. In addition to dNTM infection, 35% and 71% of our patients also suffered from salmonellosis and herpes zoster, respectively; both types of infections have rarely been reported in previous cases. This observation suggests that IFN-γ may be crucial in controlling salmonella infection and reactivating latent varicella zoster virus infection in humans. Two particular HLA alleles, DRB1*16:02 DQB1*05:02 (odds ratios of 8.68, 95% CI: 3.47-21.90, P=1.1×10-6, Pc=3.08×10-5 and 7.16, 95% CI: 3.02-17.05, P=1×10-7, Pc=1.4×10-6, respectively), were found in 82% (14/17) of our patients. In conclusion, our data suggest that anti-IFN-γ autoantibodies may play a critical role in the pathogenesis of dNTM infections and are associated with HLA-DRB1*16:02 and DQB1*05:02 among healthy adults.
- Copyright © 2013 by The American Association of Immunologists, Inc.