Anti–IFN-γ autoantibodies underlie disseminatedTalaromyces marneffeiinfections

• DOI: 10.1084/jem.20190502
• Publication Date: 2020-09-03T13:20:31Z
• Authors: Jing Guo; Xin-Qiang Ning; Jing-Ya Ding; Yan-Qing Zheng; Na-Na Shi; Feng-Yao Wu; You-Kun Lin; Han-Po Shih; He-Ting Ting; Gang Liang; Xiang-Chan Lu; Jin-Ling Kong; Ke Wang; Yi-Bo Lu; Yu-Jiao Fu; Rong Hu; Tian-Min Li; Kai-Su Pan; Xiu-Ying Li; Chun-Yang Huang; Yu-Fang Lo; Ian Yi-Feng Chang; Chun-Fu Yeh; Kun-Hua Tu; Yu-Huan Tsai; Cheng-Lung Ku; Cun-Wei Cao
• Keywords: Adult; Male; 0303 health sciences; Brief Definitive Report; Middle Aged; 3. Good health; Interferon-gamma; Young Adult; 03 medical and health sciences; Mycoses; Talaromyces; Case-Control Studies; Humans; Female; Alleles; Aged; Autoantibodies; HLA-DRB1 Chains

Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also infects individuals without known immunosuppression. Here we investigated the involvement of anti–IFN-γ autoantibodies in severe T. marneffei infections in HIV-negative patients. We enrolled 58 HIV-negative adults with severe T. marneffei infections who were otherwise healthy. We found a high prevalence of neutralizing anti–IFN-γ autoantibodies (94.8%) in this cohort. The presence of anti–IFN-γ autoantibodies was strongly associated with HLA-DRB1*16:02 and -DQB1*05:02 alleles in these patients. We demonstrated that adult-onset acquired immunodeficiency due to autoantibodies against IFN-γ is the major cause of severe T. marneffei infections in HIV-negative patients in regions where this fungus is endemic. The high prevalence of anti–IFN-γ autoantibody–associated HLA class II DRB1*16:02 and DQB1*05:02 alleles may account for severe T. marneffei infections in Southeast Asia. Our findings clarify the pathogenesis of T. marneffei infection and pave the way for developing novel treatments.