Re-exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies.
Re-exposure to beta cell autoantigens and its relevance in the presence of donor-specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty-three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2), insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8). Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA-2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post-transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p < 0.0001), 12 months (p < 0.0001), and from post-6 to post-12 months (p = 0.0002) was seen. No new BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow-up (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.
Division of Nephrology/Transplant, Department of Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Muhammad Ahmad
MA
Mujtaba
Division of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Jonathan
J
Fridell
Transplant Immunology Lab, Indiana University School of Medicine, Indianapolis, IN, USA.
Benita
B
Book
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
Sara
S
Faiz
Division of Nephrology/Transplant, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Asif
A
Sharfuddin
Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Eric
E
Wiebke
Transplant Immunology Lab, Indiana University School of Medicine, Indianapolis, IN, USA.
Mark
M
Rigby
Division of Nephrology/Transplant, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Tim
T
Taber
D064591:Allografts; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology* / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D011379:Prognosis; D011446:Prospective Studies
D001323:Autoantibodies; D001324:Autoantigens
autoantibodies; autoimmunity; donor specific antibodies; pancreas transplant; pancreatic allograft dysfunction