title: Soluble ligands for the NKG2D receptor are released during endometriosis and correlate with disease severity.
abstract: BACKGROUND
  Endometriosis is a benign gynaecological disease. Abundant bulk of evidence suggests that patients with endometriosis have an immunity dysfunction that enables ectopic endometrial cells to implant and proliferate. Previous studies show that natural killer cells have a pivotal role in the immune control of endometriosis.
  
  
  RESULTS
  This is a prospective laboratory study conducted in a tertiary-care university hospital between January 2011 and April 2013. We investigated non-pregnant, younger than 42-year-old patients (n= 202) during surgery for benign gynaecological conditions. After complete surgical exploration of the abdominopelvic cavity, 121 women with histologically proven endometriosis and 81 endometriosis-free controls women were enrolled. Patients with endometriosis were classified according to a surgical classification in three different types of endometriosis: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE). Peritoneal fluid samples were obtained from all study participants during the surgery in order to detect soluble NKG2D ligands (MICA, MICB and ULBP-2). When samples with undetectable peritoneal fluid levels of MICA, MICB and ULBP-2 were excluded, MICA ratio levels were significantly higher in endometriosis patients than in controls (median, 1.1 pg/mg; range, 0.1-143.5 versus median, 0.6 pg/mg; range, 0.1-3.5; p=0.003). In a similar manner peritoneal fluid MICB levels were also increased in endometriosis-affected patients compared with disease-free women (median, 4.6 pg/mg; range, 1.2-4702 versus median, 3.4 pg/mg; range, 0.7-20.1; p=0.001). According to the surgical classification, peritoneal fluid soluble MICA, MICB and ULBP-2 ratio levels were significantly increased in DIE as compared to controls (p=0.015, p=0.003 and p=0.045 respectively). MICA ratio levels also correlated with dysmenorrhea (r=0.232; p=0.029), total rAFS score (r=0.221; p=0.031) and adhesions rAFS score (r=0.221; p=0.031).
  
  
  CONCLUSIONS
  We demonstrate a significant increase of peritoneal fluid NKG2D ligands in women with endometriosis especially in those cases presenting DIE. This study suggests that NKG2D ligands shedding is a novel pathway in endometriosis complex pathogenesis that impairs NK cell function.
authors.affiliation: Département Développement, Reproduction et Cancer, Institut Cochin, INSERM, Paris, France; Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Department of Gynecology Obstetrics II and Reproductive Medicine, Paris, France; Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine-University of Barcelona, Barcelona, Spain.
authors.forename: Iñaki
authors.initials: I
authors.lastname: González-Foruria
authors.affiliation: Département Développement, Reproduction et Cancer, Institut Cochin, INSERM, Paris, France; Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Department of Gynecology Obstetrics II and Reproductive Medicine, Paris, France.
authors.forename: Pietro
authors.initials: P
authors.lastname: Santulli
authors.affiliation: Département Développement, Reproduction et Cancer, Institut Cochin, INSERM, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chouzenoux
authors.affiliation: Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine-University of Barcelona, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Carmona
authors.affiliation: Département Développement, Reproduction et Cancer, Institut Cochin, INSERM, Paris, France; Service d'immunologie biologique, Hôpital Cochin, Paris cedex 14, France; DHU Risque et grossesse, Hôpital Cochin, Paris cedex 14, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
authors.affiliation: Département Développement, Reproduction et Cancer, Institut Cochin, INSERM, Paris, France; Université Paris Descartes, Sorbone Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Department of Gynecology Obstetrics II and Reproductive Medicine, Paris, France; DHU Risque et grossesse, Hôpital Cochin, Paris cedex 14, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Chapron
mesh_terms: D000328:Adult; D001202:Ascitic Fluid / Q000276:immunology / Q000473:pathology*; D004715:Endometriosis / Q000276:immunology / Q000473:pathology*; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology*; D011446:Prospective Studies
chemical_list: D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; C423230:ULBP2 protein, human