PMID- 30158921 OWN - NLM STAT- MEDLINE DCOM- 20190916 LR - 20190916 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - Soluble HLA-G Expression Inversely Correlates With Fetal Microchimerism Levels in Peripheral Blood From Women With Scleroderma. PG - 1685 LID - 10.3389/fimmu.2018.01685 [doi] LID - 1685 AB - Women with scleroderma (SSc) maintain significantly higher quantities of persisting fetal microchimerism (FMc) from complete or incomplete pregnancies in their peripheral blood compared to healthy women. The non-classical class-I human leukocyte antigen (HLA) molecule HLA-G plays a pivotal role for the implantation and maintenance of pregnancy and has often been investigated in offspring from women with pregnancy complications. However data show that maternal HLA-G polymorphisms as well as maternal soluble HLA-G (sHLA-G) expression could influence pregnancy outcome. Here, we aimed to investigate the underlying role of maternal sHLA-G expression and HLA-G polymorphisms on the persistence of FMc. We measured sHLA-G levels by enzyme linked immunosorbent assay in plasma samples from 88 healthy women and 74 women with SSc. Male Mc was quantified by DYS14 real-time PCR in blood samples from 58 women who had previously given birth to at least one male child. Furthermore, eight HLA-G 5'URR/3'UTR polymorphisms, previously described as influencing HLA-G expression, were performed on DNA samples from 96 healthy women and 106 women with SSc. Peripheral sHLA-G was at lower concentration in plasma from SSc (76.2 +/- 48.3 IU/mL) compared to healthy women (117.5 +/- 60.1 IU/mL, p < 0.0001), independently of clinical subtypes, autoantibody profiles, disease duration, or treatments. Moreover, sHLA-G levels were inversely correlated to FMc quantities (Spearman correlation, p < 0.01). Finally, women with SSc had lower sHLA-G independently of the eight HLA-G 5'URR/3'UTR polymorphisms, although they were statistically more often homozygous than heterozygous for HLA-G polymorphism genotypes -716 (G/T), -201 (G/A), 14 bp (ins/del), and +3,142 (G/A) than healthy women. In conclusion, women with SSc display less sHLA-G expression independently of the eight HLA-G polymorphisms tested. This decreased production correlates with higher quantities of persisting FMc commonly observed in blood from SSc women. These results shed some lights on the contribution of the maternal HLA-G protein to long-term persistent fetal Mc and initiate new perspectives in this field. FAU - Di Cristofaro, Julie AU - Di Cristofaro J AD - Aix Marseille Univ, CNRS, EFS, ADES, "Biologie des Groupes Sanguins", Marseille, France. FAU - Karlmark, Karlin R AU - Karlmark KR AD - Aix Marseille Univ, INSERM, Autoimmune Arthritis (AA), Marseille, France. FAU - Kanaan, Sami B AU - Kanaan SB AD - Aix Marseille Univ, INSERM, Autoimmune Arthritis (AA), Marseille, France. FAU - Azzouz, Doua F AU - Azzouz DF AD - Aix Marseille Univ, INSERM, Autoimmune Arthritis (AA), Marseille, France. FAU - El Haddad, Marina AU - El Haddad M AD - Aix Marseille Univ, INSERM, Autoimmune Arthritis (AA), Marseille, France. FAU - Hubert, Lucas AU - Hubert L AD - Immunogenetics Laboratory, EFS-Alpes Mediterranee, Marseille, France. AD - Antibody Therapeutics and Immunotargeting, CRCM, INSERM U1068, Institut Paoli Calmettes, Aix-Marseille Universite, Marseille, France. AD - UM 105, CNRS UMR7258, Marseille, France. FAU - Farge-Bancel, Dominique AU - Farge-Bancel D AD - Unite de Medecine Interne Maladies Auto-immunes et Pathologie Vasculaire (UF 04) Hopital Saint Louis, AP-HP, Centre de Reference des Maladies auto-immunes systemiques Rares d'Ile-de-France, FAI2R, EA 3518, Institut Universitaire d'Hematologie, Paris, France. FAU - Granel, Brigitte AU - Granel B AD - UMR-S 1076 Endothelium, Pathologies Vasculaires et Cibles Therapeutiques - Faculte de Pharmacie, Marseille, France. AD - AP-HM, Pole de Medecine Interne, Centre de Competence PACA Ouest pour la prise en charge des maladies autoimmunes systemiques, Marseille, France. FAU - Harle, Jean Robert AU - Harle JR AD - AP-HM, Pole de Medecine Interne, Centre de Competence PACA Ouest pour la prise en charge des maladies autoimmunes systemiques, Marseille, France. FAU - Hachulla, Eric AU - Hachulla E AD - Service de Medecine Interne, Centre National de Reference de la Sclerodermie Systemique, Hopital Claude Huriez, Lille, France. FAU - Pardoux, Etienne AU - Pardoux E AD - Aix Marseille Univ, CNRS, Centrale Marseille, I2M, Marseille, France. FAU - Roudier, Jean AU - Roudier J AD - Aix Marseille Univ, INSERM, Autoimmune Arthritis (AA), Marseille, France. AD - Rhumatologie, IML, AP-HM, Hopital Sainte Marguerite, Marseille, France. FAU - Picard, Christophe AU - Picard C AD - Aix Marseille Univ, CNRS, EFS, ADES, "Biologie des Groupes Sanguins", Marseille, France. AD - Immunogenetics Laboratory, EFS-Alpes Mediterranee, Marseille, France. FAU - Lambert, Nathalie C AU - Lambert NC AD - Aix Marseille Univ, INSERM, Autoimmune Arthritis (AA), Marseille, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180814 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Autoantibodies) RN - 0 (HLA-G Antigens) RN - 0 (Untranslated Regions) SB - IM MH - Adult MH - Aged MH - Alleles MH - Autoantibodies/immunology MH - Case-Control Studies MH - *Chimerism MH - Female MH - Fetal Development/*genetics/*immunology MH - *Gene Expression MH - Gene Frequency MH - Genotype MH - HLA-G Antigens/blood/*genetics/*immunology MH - Haplotypes MH - Humans MH - Male MH - Middle Aged MH - Polymorphism, Genetic MH - Pregnancy MH - Scleroderma, Systemic/diagnosis/*genetics/*immunology/therapy MH - Untranslated Regions PMC - PMC6104483 OTO - NOTNLM OT - fetal OT - human leukocyte antigen-G OT - microchimerism OT - pregnancy OT - scleroderma OT - systemic sclerosis EDAT- 2018/08/31 06:00 MHDA- 2019/09/17 06:00 PMCR- 2018/01/01 CRDT- 2018/08/31 06:00 PHST- 2018/04/26 00:00 [received] PHST- 2018/07/09 00:00 [accepted] PHST- 2018/08/31 06:00 [entrez] PHST- 2018/08/31 06:00 [pubmed] PHST- 2019/09/17 06:00 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2018.01685 [doi] PST - epublish SO - Front Immunol. 2018 Aug 14;9:1685. doi: 10.3389/fimmu.2018.01685. eCollection 2018.