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

doi:10.1084/jem.20190502

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

Institute of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

81 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 language	English
Article number	e20190502
Journal	Journal of Experimental Medicine
Volume	217
Issue number	12
DOIs	https://doi.org/10.1084/jem.20190502
State	Published - 7 Dec 2020

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10.1084/jem.20190502

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Guo, J., Ning, X. Q., Ding, J. Y., Zheng, Y. Q., Shi, N. N., Wu, F. Y., Lin, Y. K., Shih, H. P., Ting, H. T., Liang, G., Lu, X. C., Kong, J. L., Wang, K., Lu, Y. B., Fu, Y. J., Hu, R., Li, T. M., Pan, K. S., Li, X. Y., ... Cao, C. W. (2020). Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections. Journal of Experimental Medicine, 217(12), Article e20190502. https://doi.org/10.1084/jem.20190502

@article{30aaaf6d020741798f07eeef1b8ec02d,

title = "Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections",

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.",

author = "Jing Guo and Ning, {Xin Qiang} and Ding, {Jing Ya} and Zheng, {Yan Qing} and Shi, {Na Na} and Wu, {Feng Yao} and Lin, {You Kun} and Shih, {Han Po} and Ting, {He Ting} and Gang Liang and Lu, {Xiang Chan} and Kong, {Jin Ling} and Ke Wang and Lu, {Yi Bo} and Fu, {Yu Jiao} and Rong Hu and Li, {Tian Min} and Pan, {Kai Su} and Li, {Xiu Ying} and Huang, {Chun Yang} and Lo, {Yu Fang} and Chang, {Ian Yi Feng} and Yeh, {Chun Fu} and Tu, {Kun Hua} and Tsai, {Yu Huan} and Ku, {Cheng Lung} and Cao, {Cun Wei}",

note = "Publisher Copyright: {\textcopyright} 2020 Guo et al. This article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).",

year = "2020",

month = dec,

day = "7",

doi = "10.1084/jem.20190502",

language = "English",

volume = "217",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

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Guo, J, Ning, XQ, Ding, JY, Zheng, YQ, Shi, NN, Wu, FY, Lin, YK, Shih, HP, Ting, HT, Liang, G, Lu, XC, Kong, JL, Wang, K, Lu, YB, Fu, YJ, Hu, R, Li, TM, Pan, KS, Li, XY, Huang, CY, Lo, YF, Chang, IYF, Yeh, CF, Tu, KH, Tsai, YH, Ku, CL & Cao, CW 2020, 'Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections', Journal of Experimental Medicine, vol. 217, no. 12, e20190502. https://doi.org/10.1084/jem.20190502

TY - JOUR

T1 - Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections

AU - Guo, Jing

AU - Ning, Xin Qiang

AU - Ding, Jing Ya

AU - Zheng, Yan Qing

AU - Shi, Na Na

AU - Wu, Feng Yao

AU - Lin, You Kun

AU - Shih, Han Po

AU - Ting, He Ting

AU - Liang, Gang

AU - Lu, Xiang Chan

AU - Kong, Jin Ling

AU - Wang, Ke

AU - Lu, Yi Bo

AU - Fu, Yu Jiao

AU - Hu, Rong

AU - Li, Tian Min

AU - Pan, Kai Su

AU - Li, Xiu Ying

AU - Huang, Chun Yang

AU - Lo, Yu Fang

AU - Chang, Ian Yi Feng

AU - Yeh, Chun Fu

AU - Tu, Kun Hua

AU - Tsai, Yu Huan

AU - Ku, Cheng Lung

AU - Cao, Cun Wei

N1 - Publisher Copyright: © 2020 Guo et al. This article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

PY - 2020/12/7

Y1 - 2020/12/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85090492010&partnerID=8YFLogxK

U2 - 10.1084/jem.20190502

DO - 10.1084/jem.20190502

M3 - Article

C2 - 32880631

AN - SCOPUS:85090492010

SN - 0022-1007

VL - 217

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 12

M1 - e20190502

ER -

Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections

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