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© Research
Publication : iScience

CIITA promoter polymorphism impairs monocytes HLA-DR expression in patients with septic shock.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in iScience - 18 Nov 2022

Miatello J, Lukaszewicz AC, Carter MJ, Faivre V, Hua S, Martinet KZ, Bourgeois C, Quintana-Murci L, Payen D, Boniotto M, Tissières P,

Link to Pubmed [PMID] – 36304101

Link to DOI – 10529110.1016/j.isci.2022.105291

iScience 2022 Nov; 25(11): 105291

Low monocyte (m)HLA-DR expression is associated with mortality in sepsis. G-286A∗rs3087456 polymorphism in promoter III of HLA class II transactivator (CIITA), the master regulator of HLA, has been associated with autoimmune diseases but its role in sepsis has never been demonstrated. In 203 patients in septic shock, GG genotype was associated with 28-day mortality and mHLA-DR remained low whereas it increased in patients with AA or AG genotype. In ex vivo cells, mHLA-DR failed to augment in GG in comparison with AG or AA genotype on exposure to IFN-γ. Promoter III transcript levels were similar in control monocytes regardless of genotype and exposure to IFN-γ. Promoter III activity was decreased in GG genotype in monocyte cell line but restored after stimulation with IFN-γ. Hereby, we demonstrated that G-286A∗rs3087456 significantly impact mHLA-DR expression in patients with septic shock in part through CIITA promoter III activity, that can be rescued using IFN-γ.

https://pubmed.ncbi.nlm.nih.gov/36304101