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Severe invasive infections linked to IRAK2 immune variants

Authors :
Aseervatham Anusha Amali
Kathirvel Paramasivam
Sharada Ravikumar
Zhaohong Tan
Shaun Seh Ern Loong
Kelvin Han Chung Chong
Alicia Ang
Jin Zhu
Suma Sathyanarayana Rao
Louis Yi Ann Chai
Source :
International Journal of Infectious Diseases, Vol 148, Iss , Pp 107245- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

In subjects with peculiar susceptibility to severe infections by common pyogenic bacteria, mutations of interleukin-1 receptor-associated kinase proteins (IRAK)1 and IRAK4 had been identified. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. In two patients with sequential or repeated invasive infections: herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and Streptococcus pneumoniae bacteremia with candidemia respectively, novel mutations of IRAK2 were identified. These mutations compromised the capacity to ubiquinate (or functionally modify) the signal adaptor tumor necrosis factor receptor-associated factor 6. The result is impairment of the cytokine tumor necrosis factor-alpha production. This susceptibility to a varied range of pathogens underlines a potential central role played by IRAK2 in mediating host defense in infectious diseases.

Details

Language :
English
ISSN :
12019712
Volume :
148
Issue :
107245-
Database :
Directory of Open Access Journals
Journal :
International Journal of Infectious Diseases
Publication Type :
Academic Journal
Accession number :
edsdoj.ba11468e9fea463292106d9f65d88c29
Document Type :
article
Full Text :
https://doi.org/10.1016/j.ijid.2024.107245