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Front. Immunol. | doi: 10.3389/fimmu.2018.00278

HLA-G haplotypes are differentially associated with asthmatic features

 Camille Ribeyre1,  Federico Carlini1, Céline René2, 3, François Jordier1, 4,  Christophe Picard1, 4, Jacques Chiaroni1, 4,  Laurent Abi-Rached5, Philippe Gouret6, Gregory Marin7, Nicolas Molinari7,  Pascal Chanez8, 9,  Julien Paganini6,  Delphine Gras9 and  Julie Di Cristofaro1, 4*
  • 1UMR7268 Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), France
  • 2Department of Immunology, Centre Hospitalier Universitaire de Montpellier, France
  • 3University of Montpellier 1, France
  • 4Etablissement Français du Sang Alpes Méditerranée - EFS, France
  • 5Equipe ATIP, URMITE UM63 CNRS 7278 IRD 198 INSERM 1095, IHU Mediterranee Infection, France
  • 6Xegen SAS, France
  • 7Department of Statistics, Institut Montpelliérain Alexander Grothendieck, CNRS, Univ. Montpellier, France
  • 8Clinique des Bronches, Allergie et Sommeil, Assistance Publique Hôpitaux de Marseille, France
  • 9UMR7333 Adhésion et inflammation (LAI), France

HLA-G, a HLA class Ib molecule, interacts with receptors on lymphocytes such as T cells, B cells and NK cells to influence immune responses. Unlike classical HLA molecules, HLA-G expression is not found on all somatic cells, but restricted to tissue sites, including human bronchial epithelial cells (HBEC). Individual variation of HLA-G expression is linked to its genetic polymorphism and has been associated with many pathological situations such as asthma, which is characterized by epithelium abnormalities and inflammatory cell activation. Studies reported both higher and equivalent soluble HLA-G expression in different cohorts of asthmatic patients. In particular, we recently described impaired local expression of HLA-G and abnormal profiles for alternatively spliced isoforms in HBEC from asthmatic patients.
sHLA-G dosage is challenging because of its many levels of polymorphism (dimerization, association with β2-microglobulin, and alternative splicing), thus many clinical studies focused on HLA-G SNPs as predictive biomarkers, but few analyzed HLA-G haplotypes. Here, we aimed to characterize HLA-G haplotypes and describe their association with asthmatic clinical features and sHLA-G peripheral expression, and to describe variations in transcription factor binding sites and alternative splicing sites.
HLA-G haplotypes were differentially distributed in 330 healthy and 580 asthmatic individuals. Furthermore, HLA-G haplotypes were associated with asthmatic clinical features showed. We did not however confirm an association between sHLA-G and genetic, biological or clinical parameters.
HLA-G haplotypes were phylogenetically split into distinct groups, with each group displaying particular variations in transcription factor binding or RNA splicing sites that could reflect differential HLA-G qualitative or quantitative expression, with tissue-dependent specificities.
Our results, based on a multicenter cohort, thus support the pertinence of HLA-G haplotypes as predictive genetic markers for asthma.

Keywords: HLA-G, Regulatory regions, Haplotypes, Asthma, phylogeny, Alternative Splicing

Received: 13 Nov 2017; Accepted: 31 Jan 2018.

Edited by:

Uday Kishore, Brunel University, United Kingdom

Reviewed by:

Sumati Rajagopalan, National Institute of Allergy and Infectious Diseases (NIH), United States
Silke Paust, Baylor College of Medicine, United States
Maura Rossetti, University of California, Los Angeles, United States  

Copyright: © 2018 Ribeyre, Carlini, René, Jordier, Picard, Chiaroni, Abi-Rached, Gouret, Marin, Molinari, Chanez, Paganini, Gras and Di Cristofaro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Julie Di Cristofaro, UMR7268 Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Marseille, France, julie.dicristofaro@efs.sante.fr