PMID- 29527207 OWN - NLM STAT- MEDLINE DCOM- 20190321 LR - 20190321 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - HLA-G Haplotypes Are Differentially Associated with Asthmatic Features. PG - 278 LID - 10.3389/fimmu.2018.00278 [doi] LID - 278 AB - Human leukocyte antigen (HLA)-G, a HLA class Ib molecule, interacts with receptors on lymphocytes such as T cells, B cells, and natural killer 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 epithelium cells (HBEC). Individual variation in 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 (sHLA-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 beta2-microglobulin, and alternative splicing), thus many clinical studies focused on HLA-G single-nucleotide polymorphisms 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 (TF) 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. However, we did not 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 TF 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. FAU - Ribeyre, Camille AU - Ribeyre C AD - UMR7268 Anthropologie bio-culturelle, Droit, Ethique et Sante (ADES), "Biologie des Groupes Sanguins", Aix Marseille Universite, CNRS, Etablissement Francais du Sang (EFS), Marseille, France. FAU - Carlini, Federico AU - Carlini F AD - UMR7268 Anthropologie bio-culturelle, Droit, Ethique et Sante (ADES), "Biologie des Groupes Sanguins", Aix Marseille Universite, CNRS, Etablissement Francais du Sang (EFS), Marseille, France. FAU - Rene, Celine AU - Rene C AD - Department of Immunology, CHRU de Montpellier, University Hospital Saint-Eloi, Montpellier, France. AD - Faculte de Medecine, University of Montpellier 1, Montpellier, France. FAU - Jordier, Francois AU - Jordier F AD - UMR7268 Anthropologie bio-culturelle, Droit, Ethique et Sante (ADES), "Biologie des Groupes Sanguins", Aix Marseille Universite, CNRS, Etablissement Francais du Sang (EFS), Marseille, France. AD - Etablissement Francais du Sang Alpes Mediterranee, Marseille, France. FAU - Picard, Christophe AU - Picard C AD - UMR7268 Anthropologie bio-culturelle, Droit, Ethique et Sante (ADES), "Biologie des Groupes Sanguins", Aix Marseille Universite, CNRS, Etablissement Francais du Sang (EFS), Marseille, France. AD - Etablissement Francais du Sang Alpes Mediterranee, Marseille, France. FAU - Chiaroni, Jacques AU - Chiaroni J AD - UMR7268 Anthropologie bio-culturelle, Droit, Ethique et Sante (ADES), "Biologie des Groupes Sanguins", Aix Marseille Universite, CNRS, Etablissement Francais du Sang (EFS), Marseille, France. AD - Etablissement Francais du Sang Alpes Mediterranee, Marseille, France. FAU - Abi-Rached, Laurent AU - Abi-Rached L AD - Equipe ATIP, URMITE UM63 CNRS 7278 IRD 198 INSERM 1095, IHU Mediterranee Infection, Aix Marseille Universite, Marseille, France. FAU - Gouret, Philippe AU - Gouret P AD - Xegen, Gemenos, France. FAU - Marin, Gregory AU - Marin G AD - Institut Montpellierain Alexander Grothendieck, CNRS, University of Montpellier, Montpellier, France. AD - Department of Statistics, University of Montpellier Hospitals, Montpellier, France. FAU - Molinari, Nicolas AU - Molinari N AD - Institut Montpellierain Alexander Grothendieck, CNRS, University of Montpellier, Montpellier, France. AD - Department of Statistics, University of Montpellier Hospitals, Montpellier, France. FAU - Chanez, Pascal AU - Chanez P AD - Clinique des Bronches, Allergie et Sommeil, AP-HM Hopital Nord, Marseille, France. AD - INSERM U1067, CNRS UMR 7333, Aix Marseille Universite, Marseille, France. FAU - Paganini, Julien AU - Paganini J AD - Xegen, Gemenos, France. FAU - Gras, Delphine AU - Gras D AD - INSERM U1067, CNRS UMR 7333, Aix Marseille Universite, Marseille, France. FAU - Di Cristofaro, Julie AU - Di Cristofaro J AD - UMR7268 Anthropologie bio-culturelle, Droit, Ethique et Sante (ADES), "Biologie des Groupes Sanguins", Aix Marseille Universite, CNRS, Etablissement Francais du Sang (EFS), Marseille, France. AD - Etablissement Francais du Sang Alpes Mediterranee, Marseille, France. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20180223 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Genetic Markers) RN - 0 (HLA-G Antigens) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Asthma/*genetics MH - Cohort Studies MH - Female MH - Genetic Markers/*genetics MH - HLA-G Antigens/*genetics MH - Haplotypes MH - Humans MH - Male MH - Middle Aged MH - Young Adult PMC - PMC5829031 OTO - NOTNLM OT - alternative splicing OT - asthma OT - haplotypes OT - human leukocyte antigen-G OT - phylogeny OT - regulatory regions OT - transcription factor binding site EDAT- 2018/03/13 06:00 MHDA- 2018/03/13 06:01 PMCR- 2018/01/01 CRDT- 2018/03/13 06:00 PHST- 2017/11/13 00:00 [received] PHST- 2018/01/31 00:00 [accepted] PHST- 2018/03/13 06:00 [entrez] PHST- 2018/03/13 06:00 [pubmed] PHST- 2018/03/13 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2018.00278 [doi] PST - epublish SO - Front Immunol. 2018 Feb 23;9:278. doi: 10.3389/fimmu.2018.00278. eCollection 2018.