title: Immunogenicity of Anti-HLA Antibodies in Pancreas and Islet Transplantation.
abstract: The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor-specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity, and anti-HLA antibody characteristics were collected. Between January 2008 and July 2014, 18 patients received islet transplants, and 26 patients received a pancreas transplant. Eleven out of 18 patients (61.1%) in the islet group and 12 out of 26 patients (46.2%) in the pancreas group had anti-HLA antibodies. Six patients (33.3%) developed DSAs against HLA of the islets, and 10 patients (38.4%) developed DSAs against HLA of the pancreas. Most of the DSAs were at a low level. Several parameters such as gender, number of times cells were transplanted, HLA mismatch, eplet mismatch and PIRCHE-II numbers, rejection, and infection were analyzed. Only the number of PIRCHE-II was associated with the development of anti-HLA class II de novo DSAs. Overall, the development of de novo DSAs did not influence graft survival as estimated by insulin independence. Our results indicated that pretransplant DSAs at low levels do not restrict islet or pancreas transplantation [especially islet transplantation (27.8% vs. 15.4.%)]. De novo DSAs do occur at a similar rate in both pancreas and islet transplant recipients (mainly of class II), and the immunogenicity of donor HLA is a parameter that should be taken into consideration. When combined with an immunosuppressive regimen and close follow-up, development of low levels of DSAs was not found to result in reduced graft survival or graft function in the current study.
authors.affiliation: Transplantation Immunology Unit, Service of Immunology and Allergy and Service of Laboratory Medicine, Geneva University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chaigne
authors.affiliation: Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Geneugelijk
authors.affiliation: Service of Transplantation and Visceral Surgery, Geneva University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Benoît
authors.initials: B
authors.lastname: Bédat
authors.affiliation: Service of Transplantation and Visceral Surgery, Geneva University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Mohamed Alibashe
authors.initials: MA
authors.lastname: Ahmed
authors.affiliation: Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: Gideon
authors.initials: G
authors.lastname: Hönger
authors.affiliation: Service of Nephrology, Geneva University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: De Seigneux
authors.affiliation: Service of Transplantation and Visceral Surgery, Geneva University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Demuylder-Mischler
authors.affiliation: Service of Transplantation and Visceral Surgery, Geneva University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
authors.affiliation: Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Spierings
authors.affiliation: Transplantation Immunology Unit, Service of Immunology and Allergy and Service of Laboratory Medicine, Geneva University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ferrari-Lacraz
authors.affiliation: Transplantation Immunology Unit, Service of Immunology and Allergy and Service of Laboratory Medicine, Geneva University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Jean
authors.initials: J
authors.lastname: Villard
mesh_terms: D000293:Adolescent; D000328:Adult; D000939:Epitopes / Q000276:immunology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000939:Epitopes; D006442:Glycated Hemoglobin; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies
keywords: Anti-HLA antibody; Eplet; Islet transplantation; PIRCHE; Pancreas transplantation; Sensitization