title: Alloantibody and autoantibody monitoring predicts islet transplantation outcome in human type 1 diabetes.
abstract: Long-term clinical outcome of islet transplantation is hampered by the rejection and recurrence of autoimmunity. Accurate monitoring may allow for early detection and treatment of these potentially compromising immune events. Islet transplant outcome was analyzed in 59 consecutive pancreatic islet recipients in whom baseline and de novo posttransplant autoantibodies (GAD antibody, insulinoma-associated protein 2 antigen, zinc transporter type 8 antigen) and donor-specific alloantibodies (DSA) were quantified. Thirty-nine recipients (66%) showed DSA or autoantibody increases (de novo expression or titer increase) after islet transplantation. Recipients who had a posttransplant antibody increase showed similar initial performance but significantly lower graft survival than patients without an increase (islet autoantibodies P < 0.001, DSA P < 0.001). Posttransplant DSA or autoantibody increases were associated with HLA-DR mismatches (P = 0.008), induction with antithymocyte globulin (P = 0.0001), and pretransplant panel reactive alloantibody >15% in either class I or class II (P = 0.024) as independent risk factors and with rapamycin as protective (P = 0.006) against antibody increases. DSA or autoantibody increases after islet transplantation are important prognostic markers, and their identification could potentially lead to improved islet cell transplant outcomes.
authors.affiliation: Diabetes Research Institute, San Raffaele Hospital Scientific Institute, Milan, Italy. piemonti.lorenzo@hsr.it
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Piemonti
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Everly
authors.forename: Paola
authors.initials: P
authors.lastname: Maffi
authors.forename: Marina
authors.initials: M
authors.lastname: Scavini
authors.forename: Francesca
authors.initials: F
authors.lastname: Poli
authors.forename: Rita
authors.initials: R
authors.lastname: Nano
authors.forename: Massimo
authors.initials: M
authors.lastname: Cardillo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Melzi
authors.forename: Alessia
authors.initials: A
authors.lastname: Mercalli
authors.forename: Valeria
authors.initials: V
authors.lastname: Sordi
authors.forename: Vito
authors.initials: V
authors.lastname: Lampasona
authors.forename: Alejandro
authors.initials: A
authors.lastname: Espadas de Arias
authors.forename: Mario
authors.initials: M
authors.lastname: Scalamogna
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bosi
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Antonio
authors.initials: A
authors.lastname: Secchi
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000009:adverse effects; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects* / Q000276:immunology; D007518:Isoantibodies / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives; D011379:Prognosis; D020123:Sirolimus / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D000961:Antilymphocyte Serum; D001323:Autoantibodies; D015415:Biomarkers; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D009173:Mycophenolic Acid; D020123:Sirolimus