Dominant Negative TRAF3 Variant With Recurrent Mycobacterium abscessus Infection and Bronchiectasis

Mei Fong Liew; Hui Fang Lim; Mui Cheng Liang; Ives Lim; Zhaohong Tan; Rachel Ying Min Tan; Qi Hui Sam; Win Mar Soe; Sen Hee Tay; Shengli Xu; Matthew Wook Chang; Roger Foo; Tuck Wah Soong; Sharada Ravikumar; Louis Yi Ann Chai

doi:10.1093/ofid/ofac379

Dominant Negative TRAF3 Variant With Recurrent Mycobacterium abscessus Infection and Bronchiectasis

Open Forum Infect Dis. 2022 Aug 3;9(8):ofac379. doi: 10.1093/ofid/ofac379. eCollection 2022 Aug.

Authors

Mei Fong Liew¹, Hui Fang Lim², Mui Cheng Liang³, Ives Lim⁴, Zhaohong Tan⁵, Rachel Ying Min Tan⁵, Qi Hui Sam⁵, Win Mar Soe⁵, Sen Hee Tay⁶, Shengli Xu³, Matthew Wook Chang⁷, Roger Foo⁶, Tuck Wah Soong³, Sharada Ravikumar⁵, Louis Yi Ann Chai⁶

Affiliations

¹ FAST and Chronic Programmes, Alexandra Hospital, National University Health System, Singapore, Singapore.
² Division of Respiratory and Critical Care Medicine, Department of Medicine, National University Hospital, National University Health System, Singapore, Singapore.
³ Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁴ Bioinformatics Institute, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
⁵ Division of Infectious Diseases, Department of Medicine, National University Health System, Singapore, Singapore.
⁶ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁷ Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore.

Abstract

Host factors leading to pulmonary nontuberculous mycobacteria (PNTM) disease are poorly understood compared with disseminated NTM disease, which is linked to the interleukin 12-interferon gamma signaling pathway. We investigated the tumor necrosis factor receptor associated factor 3 (TRAF3) R338W variant in a patient with recurrent PNTM infection, demonstrating TRAF3- and TNF-α-deficient phenotypes via ex vivo immune and cloning-transfection cellular studies.

Keywords: immunocompromised host; nontuberculous mycobacteria; pulmonary infection; transfection.