title: Sensitisation to swine leukocyte antigens in patients with broadly reactive HLA specific antibodies.
abstract: We have previously shown that IgG HLA specific antibodies in the sera of highly sensitised patients awaiting renal transplantation can cross-react with swine leukocyte antigens (SLA). In this study we determined the frequency of patient serum IgG HLA specific antibody binding to a porcine lymphocyte panel and the likelihood of locating a cross-match negative pig donor for sensitised patients. Serum samples (n = 82) were obtained from 35 sensitised [current IgG panel reactive antibodies (PRA) > 10%] and seven nonsensitised patients awaiting renal transplantation at Addenbrooke's Hospital, Cambridge, UK. Fifty sera had IgG HLA specific PRA of 11-84%, 20 had IgG PRA of >84% and 12 had 0% PRA (negative controls). Sera were absorbed with porcine erythrocytes to remove xenoreactive natural antibodies and tested for cross-reactive IgG HLA specific antibody binding by flow cytometry against a panel of porcine lymphocytes obtained from 23 human decay accelerating factor (hDAF) transgenic pigs. A total of 1,884 cross-match combinations were tested and 369 (20%) gave a positive porcine lymphocyte cross-match. For sera from sensitised patients with IgG PRA (11-64%), only 6 of 805 (0.75%) cross-match tests were positive. In contrast, for sera from patients with high IgG PRA (>64%), 363 of 805 (45%) cross-match tests were positive (p < 0.0001). There was no difference in the frequency of positive cross-matches between patient sera with IgG PRA 65-84% and highly sensitised patient sera with IgG PRA 85-100% [156/345 (45%) vs. 207/460 (45%)]. This study demonstrates that only patient sera with broadly reactive IgG HLA specific PRA (>64%) cross-react with porcine lymphocytes. If future clinical trials of xenotransplantation are undertaken, it may be of value to select a cross-match-negative pig organ donor for such patients.
authors.affiliation: Tissue Typing Laboratory, Addenbrooke's NHS Trust, Cambridge, UK.
authors.forename: Gertie J
authors.initials: GJ
authors.lastname: Oostingh
authors.forename: Hugh F S
authors.initials: HF
authors.lastname: Davies
authors.forename: Kerrie C G
authors.initials: KC
authors.lastname: Tang
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Bradley
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Taylor
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000276:immunology; D003429:Cross Reactions; D006680:HLA Antigens / Q000008:administration & dosage / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D013552:Swine; D017211:Treatment Failure; D014850:Waiting Lists
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies