title: Enhanced prevalence of plasmatic soluble MHC class I chain-related molecule in vascular pregnancy diseases.
abstract: The major histocompatibility complex class I related chain (MIC) is a stress-inducible protein modulating the function of immune natural killer (NK) cells, a major leukocyte subset involved in proper trophoblast invasion and spiral artery remodeling. Aim of the study was to evaluate whether upregulation of soluble MIC (sMIC) may reflect immune disorders associated to vascular pregnancy diseases (VPD). sMIC was more frequently detected in the plasma of women with a diagnostic of VPD (32%) than in normal term-matched pregnancies (1.6%, P < 0.0001), with highest prevalence in intrauterine fetal death (IUDF, 44%) and vascular intrauterine growth restriction (IUGR, 39%). sMIC levels were higher in preeclampsia (PE) than in IUFD (P < 0.01) and vascular IUGR (P < 0.05). sMIC detection was associated with bilateral early diastolic uterine notches (P = 0.037), thrombocytopenia (P = 0.03), and high proteinuria (P = 0.03) in PE and with the vascular etiology of IUGR (P = 0.0038). Incubation of sMIC-positive PE plasma resulted in downregulation of NKG2D expression and NK cell-mediated IFN-γ production in vitro. Our work thus suggests that detection of sMIC molecule in maternal plasma may constitute a hallmark of altered maternal immune functions that contributes to vascular disorders that complicate pregnancy, notably by impairing NK-cell mediated production of IFN-γ, an essential cytokine favoring vascular modeling.
authors.affiliation: Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université, Department of Gynecology and Obstetrics, Gynépole Marseille, Hôpital Nord, Chemin des Bourrely, 13915 Marseille, France ; Aix-Marseille Université, UMR 1076 INSERM, Vascular Research Center of Marseille, 3005 Marseille, France.
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Haumonte
authors.affiliation: Assistance Publique Hôpitaux de Paris, Immunology Department, Hôpital Robert Debré UMR 1149 INSERM-Université Paris Diderot, 75019 Paris, France.
authors.forename: Sophie
authors.identifier: 0000-0002-4535-3550
authors.initials: S
authors.lastname: Caillat-Zucman
authors.affiliation: Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université, Department of Gynecology and Obstetrics, Gynépole Marseille, Hôpital Nord, Chemin des Bourrely, 13915 Marseille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Bretelle
authors.affiliation: Assistance Publique Hôpitaux de Paris, Immunology Department, Hôpital Robert Debré UMR 1149 INSERM-Université Paris Diderot, 75019 Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Lambert
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Hematology Department, Secteur de Biologie Vasculaire, Hôpital Conception, 13005 Marseille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Lyonnet
authors.affiliation: Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université Materno-fœtal Biology Unit, Secteur Nord, 13916 Marseille, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Levy-Mozziconacci
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Immunology Department, Hôpital de la Conception, 13005 Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Farnarier
authors.affiliation: Assistance Publique-Hôpitaux de Marseille, Department of Gynecology and Obstetrics, Hôpital Conception, 13005 Marseille, France.
authors.forename: Agostini
authors.initials: A
authors.lastname: Aubert
authors.affiliation: Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université, Department of Gynecology and Obstetrics, Gynépole Marseille, Hôpital Nord, Chemin des Bourrely, 13915 Marseille, France.
authors.forename: Leon
authors.initials: L
authors.lastname: Boubli
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Hematology Department, Secteur de Biologie Vasculaire, Hôpital Conception, 13005 Marseille, France ; Assistance Publique Hôpitaux de Marseille, Hematology Department, Hôpital Timone, 13005 Marseille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin-Jau
authors.affiliation: Aix-Marseille Université, UMR 1076 INSERM, Vascular Research Center of Marseille, 3005 Marseille, France ; Assistance Publique Hôpitaux de Marseille, Hematology Department, Secteur de Biologie Vasculaire, Hôpital Conception, 13005 Marseille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat George
authors.affiliation: Aix-Marseille Université, UMR 1076 INSERM, Vascular Research Center of Marseille, 3005 Marseille, France ; Assistance Publique Hôpitaux de Marseille, Hematology Department, Secteur de Biologie Vasculaire, Hôpital Conception, 13005 Marseille, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Paul
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000453:epidemiology; D015395:Histocompatibility Antigens Class I / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D007694:Killer Cells, Natural; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000032:analysis / Q000378:metabolism; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood* / Q000453:epidemiology*; D011507:Proteinuria / Q000097:blood / Q000453:epidemiology; D013921:Thrombocytopenia / Q000097:blood / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D007371:Interferon-gamma