title: HLA class I sensitization in islet transplant recipients: report from the Collaborative Islet Transplant Registry.
abstract: Pancreatic islet transplantation is a promising treatment option for patients severely affected with type 1 diabetes. This report from CITR presents pre- and posttransplant human leukocyte antigen (HLA) class I sensitization rates in islet-alone transplantation. Data came from 303 recipients  transplanted with islet-alone between January 1999 and December 2008. HLA class I sensitization was determined by the presence of anti-HLA class I antibodies. Panel-reactive antibodies (PRA) from prior to islet infusion and at 6 months, and yearly posttransplant was correlated to measures  of islet graft failure. The cumulative number of mismatched HLA alleles increased with each additional islet infusion from a median of 3 for one infusion to 9 for three infusions. Pretransplant PRA was not predictive of islet graft failure. However, development of PRA >20% posttransplant  was associated with 3.6-fold (p < 0.001) increased hazard ratio for graft failure. Patients with complete graft loss who had discontinued immunosuppression had significantly higher rate of PRA ≥ 20% compared to those with functioning grafts who remained on immunosuppression. Exposure  to repeat HLA class I mismatch at second or third islet infusions resulted in less frequent development of de novo HLA class I antibodies when compared to increased class I mismatch. The development of HLA class I antibodies while on immunosuppression is associated with subsequent islet graft  failure. The risk of sensitization may be reduced by minimizing the number of islet donors used per recipient, and in the absence of donor-specific anti-HLA antibodies, repeating HLA class I mismatches with subsequent islet infusions.
authors.affiliation: Baylor Simmons Transplant Institute, Dallas, TX 75246, USA. bashoon@baylorhealth.edu
authors.forename: Bashoo
authors.initials: B
authors.lastname: Naziruddin
authors.forename: Steve
authors.initials: S
authors.lastname: Wease
authors.forename: Donald
authors.initials: D
authors.lastname: Stablein
authors.forename: Franca B
authors.initials: FB
authors.lastname: Barton
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rickels
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Alejandro
mesh_terms: D000328:Adult; D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006650:Histocompatibility Testing; D006801:Humans; D016381:Islets of Langerhans Transplantation; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012042:Registries; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies
references.citation: Am J Med Sci. 1997 May;313(5):275-8
references.pmid: 9145036
references.citation: Transplantation. 2008 Dec 27;86(12):1783-8
references.pmid: 19104422
references.citation: J Clin Endocrinol Metab. 2007 Jul;92(7):2410-4
references.pmid: 17488791
references.citation: Transplantation. 2006 Jul 27;82(2):180-7
references.pmid: 16858280
references.citation: Transplantation. 2008 Aug 15;86(3):384-90
references.pmid: 18698240
references.citation: Am J Transplant. 2008 Oct;8(10):1990-7
references.pmid: 18828765
references.citation: Transplantation. 2000 Jul 15;70(1):220-2
references.pmid: 10919608
references.citation: N Engl J Med. 2008 Aug 28;359(9):977-9
references.pmid: 18753660
references.citation: Transplantation. 2008 Jul 27;86(2):357-9
references.pmid: 18645502
references.citation: Ther Drug Monit. 2005 Feb;27(1):35-7
references.pmid: 15665744
references.citation: N Engl J Med. 2008 Dec 18;359(25):2729; author reply 2729-31
references.pmid: 19092163
references.citation: Transplantation. 2007 Sep 27;84(6):722-8
references.pmid: 17893605
references.citation: Am J Transplant. 2007 Oct;7(10):2311-7
references.pmid: 17845564
references.citation: Transplant Proc. 1979 Mar;11(1):560-2
references.pmid: 109967
references.citation: Am J Transplant. 2007 May;7(5):1242-8
references.pmid: 17456201
references.citation: Clin Transpl. 2006;:413-20
references.pmid: 18365398
references.citation: Transplantation. 1999 Nov 27;68(10):1542-6
references.pmid: 10589952
references.citation: Transplant Proc. 1997 Jun;29(4):2268-9
references.pmid: 9193621
references.citation: Diabetes. 2005 Jun;54(6):1755-62
references.pmid: 15919797
references.citation: Diabetes. 2005 Jul;54(7):2060-9
references.pmid: 15983207
references.citation: Transplant Proc. 2005 Oct;37(8):3438-40
references.pmid: 16298621
references.citation: Transplantation. 2008 Jul 27;86(2):204-5
references.pmid: 18645479
references.citation: N Engl J Med. 2006 Sep 28;355(13):1397-9
references.pmid: 17005967
references.citation: Transplantation. 2007 Dec 15;84(11):1413-27
references.pmid: 18091517
references.citation: Cell Transplant. 2009;18(7):753-67
references.pmid: 19796497
references.citation: Transplantation. 1996 Apr 27;61(8):1272-4
references.pmid: 8610431
references.citation: Am J Transplant. 2008 Nov;8(11):2463-70
references.pmid: 18808408