title: Anti-Donor HLA Antibody Response After Pancreatic Islet Grafting: Characteristics, Risk Factors, and Impact on Graft Function.
abstract: Pancreatic islet grafting restores endogenous insulin production in type 1 diabetic patients, but long-term outcomes remain disappointing as a result of immunological destruction of allogeneic islets. In solid organ transplantation, donor-specific anti-HLA antibodies (DSA) are the first cause of organ failure. This retrospective multicentric study aimed at providing in-depth characterization of DSA response after pancreatic islet grafting, identifying the risk factor for DSA generation and determining the impact of DSA on graft function. Forty-two pancreatic islet graft recipients from the Groupe Rhin-Rhône-Alpes-Genève pour la Greffe d'Ilots de Langerhans consortium were enrolled. Pre- and postgrafting sera were screened for the presence of DSA and their ability to activate complement. Prevalence of DSA was 25% at 3 years postgrafting. The risk of sensitization increased steeply after immunosuppressive drug withdrawal. DSA repertoire diversity correlated with the number of HLA and eplet mismatches. DSA titer was significantly lower from that observed in solid organ transplantation. No detected DSA bound the complement fraction C3d. Finally, in contrast with solid organ transplantation, DSA did not seem to negatively affect pancreatic islet graft survival. This might be due to the low DSA titers, specific features of IgG limiting their ability to activate the complement and/or the lack of allogenic endothelial targets in pancreatic islet grafts.
authors.affiliation: Hospices Civils de Lyon, Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Lyon, France.|INSERM U1111, Université de Lyon, Lyon, France.
authors.forename: E
authors.initials: E
authors.lastname: Pouliquen
authors.affiliation: Hôpitaux Universitaires de Strasbourg, Service d'Endocrinologie Diabète et Maladies Métaboliques, Pôle MIRNED, EA 7293 Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.
authors.forename: P
authors.initials: P
authors.lastname: Baltzinger
authors.affiliation: Hôpitaux Universitaires de Strasbourg, Service d'Endocrinologie Diabète et Maladies Métaboliques, Pôle MIRNED, EA 7293 Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.
authors.forename: A
authors.initials: A
authors.lastname: Lemle
authors.affiliation: INSERM U1111, Université de Lyon, Lyon, France.
authors.forename: C-C
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Laboratoire d' histocompatibilité, Etablissement Français de Sang, Strasbourg, France.
authors.forename: A
authors.initials: A
authors.lastname: Parissiadis
authors.affiliation: Centre Hospitalier Universitaire Jean Minjoz, Service d'Endocrinologie-Métabolisme et Diabétologie-Nutrition, Besançon, France.
authors.forename: S
authors.initials: S
authors.lastname: Borot
authors.affiliation: Centre Hospitalier Universitaire de Nancy, Service de Néphrologie, Nancy, France.
authors.forename: L
authors.initials: L
authors.lastname: Frimat
authors.affiliation: Centre Hospitalier Universitaire de Nancy, Service de Néphrologie, Nancy, France.
authors.forename: S
authors.initials: S
authors.lastname: Girerd
authors.affiliation: Departement of Surgery, Islet Isolation, and Transplantation Center, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Berney
authors.affiliation: Departement of Surgery, Islet Isolation, and Transplantation Center, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Lablanche
authors.affiliation: Département d'Endocrinologie, Pôle DigiDune, Hôpital Universitaire de Grenoble, Université Grenoble Alpes, Grenoble, France.
authors.forename: P Y
authors.initials: PY
authors.lastname: Benhamou
authors.affiliation: Hospices Civils de Lyon, Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Lyon, France.|INSERM U1111, Université de Lyon, Lyon, France.
authors.forename: E
authors.initials: E
authors.lastname: Morelon
authors.affiliation: Hospices Civils de Lyon, Service d'Urologie et de Chirurgie de la Transplantation, Pôle Chirurgie, Hôpital Edouard Herriot, Lyon, France.
authors.forename: L
authors.initials: L
authors.lastname: Badet
authors.affiliation: Laboratoire d'Histocompatibilité, Etablissement Français du Sang, Lyon, France.
authors.forename: V
authors.initials: V
authors.lastname: Dubois
authors.affiliation: Hôpitaux Universitaires de Strasbourg, Service d'Endocrinologie Diabète et Maladies Métaboliques, Pôle MIRNED, EA 7293 Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.
authors.forename: L
authors.initials: L
authors.lastname: Kessler
authors.affiliation: Hospices Civils de Lyon, Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Lyon, France.|INSERM U1111, Université de Lyon, Lyon, France.
authors.forename: O
authors.initials: O
authors.lastname: Thaunat
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology* / Q000473:pathology; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects*; D007518:Isoantibodies / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: alloantibody; clinical research/practice; islet transplantation; rejection: antibody-mediated (ABMR)