title: Pretransplant HLA antibodies are associated with reduced graft survival after clinical islet transplantation.
abstract: Despite significant improvements in islet transplantation, long-term graft function is still not optimal. It is likely that both immune and nonimmune factors are involved in the deterioration of islet function over time. Historically, the pretransplant T-cell crossmatch and antibody screening were done by anti-human globulin--complement-dependent cytotoxicity (AHG-CDC). Class II antibodies were not evaluated. In 2003, we introduced solid-phase antibody screening using flow-based beads and flow crossmatching. We were interested to know whether pretransplant human leukocyte antigen (HLA) antibodies or a positive flow crossmatch impacted islet function post-transplant. A total of 152 islet transplants was performed in 81 patients. Islet function was determined by a positive C-peptide. Results were analyzed by procedure. Class I and class II panel reactive antibody (PRA) > 15% and donor-specific antibodies (DSA) were associated with a reduced C-peptide survival (p<0.0001 and p<0.0001, respectively). A positive T- and or B-cell crossmatch alone was not. Pretransplant HLA antibodies detectable by flow beads are associated with reduced graft survival. This suggests that the sirolimus and low-dose tacrolimus-based immunosuppression may not control the alloimmune response in this presensitized population and individuals with a PRA > 15% may require more aggressive inductive and maintenance immunosuppression, or represent a group that may not benefit from islet transplantation.
authors: Department of Medicine, Division of Nephrology and Immunology, University of Alberta, Capital Health, Edmonton, Alberta, Canada. trish.campbell@ualberta.ca
authors: P M
authors: PM
authors: Campbell
authors: A
authors: A
authors: Salam
authors: E A
authors: EA
authors: Ryan
authors: P
authors: P
authors: Senior
authors: B W
authors: BW
authors: Paty
authors: D
authors: D
authors: Bigam
authors: T
authors: T
authors: McCready
authors: A
authors: A
authors: Halpin
authors: S
authors: S
authors: Imes
authors: F
authors: F
authors: Al Saif
authors: J R T
authors: JR
authors: Lakey
authors: A M J
authors: AM
authors: Shapiro
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002096:C-Peptide / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D016016:Proportional Hazards Models; D020123:Sirolimus / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000961:Antilymphocyte Serum; D002096:C-Peptide; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus