Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections
| Autor: | Ian Yi Feng Chang, Yu Fang Lo, Kai Su Pan, Kun Hua Tu, Xiang Chan Lu, Tian Min Li, Yu Jiao Fu, Cun Wei Cao, Ke Wang, Yi Bo Lu, You Kun Lin, Jing Guo, Na Na Shi, Yu Huan Tsai, Chun-Fu Yeh, Jin Ling Kong, Cheng-Lung Ku, Xin Qiang Ning, Xiu Ying Li, Han Po Shih, He Ting Ting, Rong Hu, Feng Yao Wu, Jing Ya Ding, Yan Qing Zheng, Gang Liang, Chun-Yang Huang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Hla class ii Adult Male South china medicine.medical_treatment 030106 microbiology Immunology Pathogenesis Infectious Disease and Host Defense 03 medical and health sciences Interferon-gamma Young Adult Acquired immunodeficiency syndrome (AIDS) medicine Immunology and Allergy Humans Immunodeficiency Talaromyces marneffei Alleles Aged Autoantibodies High prevalence business.industry Autoantibody Brief Definitive Report Immunosuppression Middle Aged medicine.disease 030104 developmental biology Mycoses Talaromyces Case-Control Studies Female business HLA-DRB1 Chains |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 |
| Popis: | Neutralizing anti–IFN-γ autoantibodies are the underlying immunodeficiency that explains the susceptibility to Talaromyces marneffei infections in otherwise healthy individuals in epidemic regions. This finding reveals the critical role of the IFN-γ pathway in controlling this dimorphic fungus. 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. |
| Databáze: | OpenAIRE |
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