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Increased Inflammatory Responses in Patients With Active Disseminated Non-Tuberculous Mycobacterial Infection and High Anti-Interferon-Gamma Autoantibodies

  • Pattaraporn Srisai (Department of Microbiology, Faculty of Medicine, Khon Kaen University) ;
  • Chanchai Hongsa (Department of Microbiology, Faculty of Medicine, Khon Kaen University) ;
  • Yothin Hinwan (Department of Microbiology, Faculty of Medicine, Khon Kaen University) ;
  • Varis Manbenmad (Department of Microbiology, Faculty of Medicine, Khon Kaen University) ;
  • Ploenchan Chetchotisakd (Department of Medicine, Faculty of Medicine Khon Kaen University) ;
  • Siriluck Anunnatsiri (Department of Medicine, Faculty of Medicine Khon Kaen University) ;
  • Kiatichai Faksri (Department of Microbiology, Faculty of Medicine, Khon Kaen University) ;
  • Todsapol Techo (Department of Biology, Faculty of Science, Khon Kaen University) ;
  • Kanin Salao (Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Steven W. Edwards (Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool) ;
  • Arnone Nithichanon (Department of Microbiology, Faculty of Medicine, Khon Kaen University)
  • Received : 2024.07.16
  • Accepted : 2024.09.06
  • Published : 2024.10.31
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Abstract

Adult-onset immunodeficiency (AOID) is associated with the presence of anti-IFN-γ autoantibodies (auAbs). In disseminated nontuberculous mycobacterial (dNTM) infection with AOID, neutralization of IFN-γ by auAb may play a role in disease susceptibility, but other molecular mechanisms are likely to contribute. In this study, dNTM patients, including inactive, active but non-progressive and active, progressive cases were enrolled to measure plasma anti-IFN-γ auAb by ELISA and underwent whole-blood RNA sequencing. Healthy control individuals were also enrolled. Plasma IL-8 was then quantified to confirm transcriptomic analysis. Results revealed that anti-IFN-γ auAb titers were significantly increased in patients with active stage of disease. Gene expression could separate patients with active infection from individuals with no signs of infection (inactive patients and healthy controls). In active cases, there was over-expression of inflammatory pathways and under-expression of type-2 immunity pathways. Interestingly, increased levels of plasma IL-8 (p=0.0167) not only confirmed gene expression results but also correlated with the presence of neutrophilic dermatitis (p=0.0244). In conclusion, our findings highlight the value of anti-IFN-γ auAb titers for predicting disease reactivity and first propose IL-8 as a promising mediator to be further explored, given its correlation with skin reactive disease, a hallmark of active dNTM infection.

Keywords

Acknowledgement

This work was supported by the National Research Council of Thailand (NRCT) under contract no. N42A650205. We acknowledge the medical staffs at Srinagarind Hospital, Khon Kaen University, Thailand, for assisting and reviewing patient records. We would like to acknowledge Prof.David Blair for editing the manuscript via Publication Clinic KKU, Thailand.

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