Alloantibody and Autoantibody Monitoring Predicts Islet Transplantation Outcome in Human Type 1 Diabetes

  1. Paul I. Terasaki2
  1. 1Diabetes Research Institute, San Raffaele Hospital Scientific Institute, Milan, Italy
  2. 2Terasaki Foundation Laboratory, Los Angeles, California
  3. 3Organ and Tissue Transplantation Immunology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
  4. 4Center for Translational Genomics and Bioinformatics, Milan, Italy
  5. 5Vita-Salute San Raffaele University, Milan, Italy
  6. 6Center for Regenerative Therapies and Paul Langerhans Institute Dresden, Dresden University of Technology, Dresden, Germany
  1. Corresponding author: Lorenzo Piemonti, piemonti.lorenzo{at}hsr.it.
  1. E.Bon., A.S., and P.I.T. contributed equally to this study.

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.

Footnotes

  • Received September 12, 2012.
  • Accepted November 17, 2012.

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  1. Diabetes vol. 62 no. 5 1656-1664
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