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

Jordi Miatello; Anne-Claire Lukaszewicz; Michael J. Carter; Valérie Faivre; Stéphane Hua; Kim Z. Martinet; Christine Bourgeois; Lluis Quintana-Murci; Didier Payan; Michele Boniotto; Tissières Pierre

doi:10.1016/j.isci.2022.105291

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

Jordi Miatello, Anne-Claire Lukaszewicz, Michael J. Carter, Valérie Faivre, Stéphane Hua, Kim Z. Martinet, Christine Bourgeois, Lluis Quintana-Murci, Didier Payan, Michele Boniotto, Tissières Pierre

Women & Children's Health

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Abstract

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.

Original language	English
Article number	105291
Pages (from-to)	105291
Journal	iScience
Volume	25
Issue number	11
Early online date	20 Oct 2022
DOIs	https://doi.org/10.1016/j.isci.2022.105291
Publication status	Published - 18 Nov 2022

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CIITA promoter polymorphism impairs_MIATELLO_Publishedonline20October2022_GOLD VoR (CC BY-NC-ND)Final published version, 1.83 MBLicence: CC BY-NC-ND

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@article{60c1a444f369410995ed66164a8247de,

title = "CIITA promoter polymorphism impairs monocytes HLA-DR expression in patients with septic shock",

abstract = "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.",

author = "Jordi Miatello and Anne-Claire Lukaszewicz and Carter, {Michael J.} and Val{\'e}rie Faivre and St{\'e}phane Hua and Martinet, {Kim Z.} and Christine Bourgeois and Lluis Quintana-Murci and Didier Payan and Michele Boniotto and Tissi{\`e}res Pierre",

note = "Funding Information: We thank Sergio Crovella (Department of Advanced Diagnostics, Institute for Maternal and Child Health-IRCCS 'Burlo Garofolo', Trieste, Italy and Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy) for help with paper revisions. The study was supported by a BQR “ Bonus Qualit{\'e} Recherche ” grant from the University Paris Sud to P.T. Funding Information: We thank Sergio Crovella (Department of Advanced Diagnostics, Institute for Maternal and Child Health-IRCCS 'Burlo Garofolo', Trieste, Italy and Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy) for help with paper revisions. The study was supported by a BQR “Bonus Qualit{\'e} Recherche” grant from the University Paris Sud to P.T. Investigation, J.M. M.B. S.H. K.Z.M. C.B. V.F. A.C.L. and D.P.; Formal analysis and Visualization, J.M. M.J.C. M.B. and P.T.; Conceptualization and Methodology, J.M. M.B. P.T. D.P. and A.C.L.; Writing – Original Draft, J.M. P.T. and M.B.; Writing – Review and Editing, J.M. P.T. M.J.C. and M.B. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",

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doi = "10.1016/j.isci.2022.105291",

language = "English",

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T1 - CIITA promoter polymorphism impairs monocytes HLA-DR expression in patients with septic shock

AU - Miatello, Jordi

AU - Lukaszewicz, Anne-Claire

AU - Carter, Michael J.

AU - Faivre, Valérie

AU - Hua, Stéphane

AU - Martinet, Kim Z.

AU - Bourgeois, Christine

AU - Quintana-Murci, Lluis

AU - Payan, Didier

AU - Boniotto, Michele

AU - Pierre, Tissières

N1 - Funding Information: We thank Sergio Crovella (Department of Advanced Diagnostics, Institute for Maternal and Child Health-IRCCS 'Burlo Garofolo', Trieste, Italy and Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy) for help with paper revisions. The study was supported by a BQR “ Bonus Qualité Recherche ” grant from the University Paris Sud to P.T. Funding Information: We thank Sergio Crovella (Department of Advanced Diagnostics, Institute for Maternal and Child Health-IRCCS 'Burlo Garofolo', Trieste, Italy and Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy) for help with paper revisions. The study was supported by a BQR “Bonus Qualité Recherche” grant from the University Paris Sud to P.T. Investigation, J.M. M.B. S.H. K.Z.M. C.B. V.F. A.C.L. and D.P.; Formal analysis and Visualization, J.M. M.J.C. M.B. and P.T.; Conceptualization and Methodology, J.M. M.B. P.T. D.P. and A.C.L.; Writing – Original Draft, J.M. P.T. and M.B.; Writing – Review and Editing, J.M. P.T. M.J.C. and M.B. The authors declare no competing interests. Publisher Copyright: © 2022 The Authors

PY - 2022/11/18

Y1 - 2022/11/18

N2 - 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.

AB - 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.

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U2 - 10.1016/j.isci.2022.105291

DO - 10.1016/j.isci.2022.105291

M3 - Article

SN - 2589-0042

VL - 25

SP - 105291

JO - iScience

JF - iScience

IS - 11

M1 - 105291

ER -

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

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