Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections

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 HuangYu Fang Lo, Ian Yi Feng Chang, Chun Fu Yeh, Kun Hua Tu, Yu Huan Tsai, Cheng Lung Ku*, Cun Wei Cao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere20190502
JournalJournal of Experimental Medicine
Volume217
Issue number12
DOIs
StatePublished - 7 Dec 2020

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