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Influence of HLA-C environment on the spontaneous clearance of hepatitis C in European HIV-HCV co-infected individuals
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  • Nolwenn Legrand,
  • Gaëlle David,
  • Audrey Rodallec,
  • Aurélie Gaultier,
  • Dominique Salmon,
  • Anne Cesbron,
  • Linda Wittkop,
  • François Raffi,
  • Ketevan Gendzekhadze,
  • Christelle Retiere,
  • Clotilde Allavena,
  • Katia Gagne
Nolwenn Legrand
EFS

Corresponding Author:nolwenn.legrand@efs.sante.fr

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Gaëlle David
Etablissement Français du Sang
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Audrey Rodallec
CHU Hotel Dieu
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Aurélie Gaultier
CHU Hotel Dieu
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Dominique Salmon
APHP
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Anne Cesbron
EFS
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Linda Wittkop
CHU
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François Raffi
CHU Hotel Dieu
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Ketevan Gendzekhadze
City of Hope medican center
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Christelle Retiere
Etablissement Fraçais du Sang
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Clotilde Allavena
CHU Hotel Dieu
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Katia Gagne
EFS
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Abstract

Natural Killer (NK) cell functions are regulated by diverse inhibitory and activating receptors including Killer cell Immunoglobulin-like receptors (KIR) which interact with HLA class I molecules. Some KIR/HLA genetic combinations were reported associated with spontaneous clearance (SC) of hepatitis C virus (HCV) but with discordant results, possibly reflecting KIR and/or HLA gene polymorphism according to populations. KIR/HLA genetic combinations associated with both an exhaustive NK and T cell repertoire were investigated in a cohort of HIV-HCV co-infected individuals with either SC (n=68) or chronic infection (CI, n=163) compared to uninfected blood donors (Ctrl, n=100). Multivariate analysis showed that the HLA C2C2 environment was associated with SC only in European HIV-HCV co-infected individuals (OR=4.30[1.57-12.25], p=0.005). KIR2D+ NK cell repertoire and potential of degranulation of KIR2DL1/S1+ NK cells were similar in SC European cohort compared to uninfected individuals. In contrast, decreased frequencies of KIR2DS1+ and KIR2DL2+ NK cells were detected in CI group of Europeans compared to SC and a decreased frequency of KIR2DL1/S1+ NK cells compared to controls. On the T cell side, higher frequencies of DNAM-1+ and CD57+ T cells were observed in SC in comparison to controls. Interestingly, SC subjects emphasized increased frequencies of KIR2DL2/L3/S2+ T cells compared to CI subjects. Our study underlines that the C2 environment may activate efficient KIR2DL1+ NK cells in viral context and maintain KIR2DL2/L3/S2+ mature T cell response in the absence of KIR2DL2 engagement with its cognate ligands in SC group of HCV-HIV co-infected European patients.
05 Aug 2020Submitted to Clinical & Experimental Immunology
05 Aug 2020Submission Checks Completed
05 Aug 2020Assigned to Editor
21 Aug 2020Reviewer(s) Assigned
06 Oct 2020Review(s) Completed, Editorial Evaluation Pending
20 Oct 2020Editorial Decision: Revise Minor
09 Nov 20201st Revision Received
10 Nov 2020Reviewer(s) Assigned
17 Nov 2020Review(s) Completed, Editorial Evaluation Pending
20 Nov 2020Editorial Decision: Revise Major
26 Nov 20202nd Revision Received
26 Nov 2020Reviewer(s) Assigned
04 Dec 2020Review(s) Completed, Editorial Evaluation Pending
07 Dec 2020Editorial Decision: Revise Minor
07 Dec 20203rd Revision Received
07 Dec 2020Review(s) Completed, Editorial Evaluation Pending
07 Dec 2020Editorial Decision: Accept
10 Mar 2021Published in Clinical and Experimental Immunology volume 204 issue 1 on pages 107-124. 10.1111/cei.13562