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

Overview

Journal Diabetes

Specialty Endocrinology

Date 2013 Jan 1

PMID 23274902

Citations 48

Authors

Lorenzo Piemonti

Matthew J Everly

Paola Maffi

Marina Scavini

Francesca Poli

Rita Nano

Massimo Cardillo

Raffaella Melzi

Alessia Mercalli

Valeria Sordi

Vito Lampasona

Alejandro Espadas de Arias

Mario Scalamogna

Emanuele Bosi

Ezio Bonifacio

Antonio Secchi

Paul I Terasaki

Affiliations

Soon will be listed here.

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.

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References

Kerman R, Susskind B, Buyse I, Pryzbylowski P, Ruth J, Warnell S . Flow cytometry-detected IgG is not a contraindication to renal transplantation: IgM may be beneficial to outcome. Transplantation. 2000; 68(12):1855-8. DOI: 10.1097/00007890-199912270-00007. View

Ferrari-Lacraz S, Berney T, Morel P, Marangon N, Hadaya K, Demuylder-Mischler S . Low risk of anti-human leukocyte antigen antibody sensitization after combined kidney and islet transplantation. Transplantation. 2008; 86(2):357-9. DOI: 10.1097/TP.0b013e31817ba628. View

Kessler L, Parissiadis A, Bayle F, Moreau F, Pinget M, Froelich N . Evidence for humoral rejection of a pancreatic islet graft and rescue with rituximab and IV immunoglobulin therapy. Am J Transplant. 2009; 9(8):1961-6. DOI: 10.1111/j.1600-6143.2009.02711.x. View

Huurman V, Velthuis J, Hilbrands R, Tree T, Gillard P, van der Meer-Prins P . Allograft-specific cytokine profiles associate with clinical outcome after islet cell transplantation. Am J Transplant. 2008; 9(2):382-8. DOI: 10.1111/j.1600-6143.2008.02479.x. View

McAlister C, Gao Z, McAlister V, Gupta R, Wright Jr J, Macdonald A . Protective anti-donor IgM production after crossmatch positive liver-kidney transplantation. Liver Transpl. 2004; 10(2):315-9. DOI: 10.1002/lt.20062. View

Rickels M, Kamoun M, Kearns J, Markmann J, Naji A . Evidence for allograft rejection in an islet transplant recipient and effect on beta-cell secretory capacity. J Clin Endocrinol Metab. 2007; 92(7):2410-4. DOI: 10.1210/jc.2007-0172. View

Bonifacio E, Genovese S, Braghi S, Bazzigaluppi E, Lampasona V, Bingley P . Islet autoantibody markers in IDDM: risk assessment strategies yielding high sensitivity. Diabetologia. 1995; 38(7):816-22. DOI: 10.1007/s001250050358. View

Lampasona V, Petrone A, Tiberti C, Capizzi M, Spoletini M, di Pietro S . Zinc transporter 8 antibodies complement GAD and IA-2 antibodies in the identification and characterization of adult-onset autoimmune diabetes: Non Insulin Requiring Autoimmune Diabetes (NIRAD) 4. Diabetes Care. 2009; 33(1):104-8. PMC: 2797953. DOI: 10.2337/dc08-2305. View

Achenbach P, Bonifacio E, Koczwara K, Ziegler A . Natural history of type 1 diabetes. Diabetes. 2005; 54 Suppl 2:S25-31. DOI: 10.2337/diabetes.54.suppl_2.s25. View

10.

Fradet Y, Roy R, Lachance J, Noel R . Kidney graft survival: role of blood transfusions and lymphocytotoxic antibodies. Clin Nephrol. 1982; 18(2):69-73. View

11.

Occhipinti M, Lampasona V, Vistoli F, Bazzigaluppi E, Scavini M, Boggi U . Zinc transporter 8 autoantibodies increase the predictive value of islet autoantibodies for function loss of technically successful solitary pancreas transplant. Transplantation. 2011; 92(6):674-7. DOI: 10.1097/TP.0b013e31822ae65f. View

12.

Roelen D, Huurman V, Hilbrands R, Gillard P, Duinkerken G, van der Meer-Prins P . Relevance of cytotoxic alloreactivity under different immunosuppressive regimens in clinical islet cell transplantation. Clin Exp Immunol. 2009; 156(1):141-8. PMC: 2673752. DOI: 10.1111/j.1365-2249.2008.03812.x. View

13.

Gebel H, Bray R . The evolution and clinical impact of human leukocyte antigen technology. Curr Opin Nephrol Hypertens. 2010; 19(6):598-602. DOI: 10.1097/MNH.0b013e32833dfc3f. View

14.

Sibley R, Sutherland D, Goetz F, Michael A . Recurrent diabetes mellitus in the pancreas iso- and allograft. A light and electron microscopic and immunohistochemical analysis of four cases. Lab Invest. 1985; 53(2):132-44. View

15.

Jaeger C, Brendel M, Hering B, Eckhard M, Bretzel R . Progressive islet graft failure occurs significantly earlier in autoantibody-positive than in autoantibody-negative IDDM recipients of intrahepatic islet allografts. Diabetes. 1997; 46(11):1907-10. DOI: 10.2337/diab.46.11.1907. View

16.

Kellar K, Iannone M . Multiplexed microsphere-based flow cytometric assays. Exp Hematol. 2002; 30(11):1227-37. DOI: 10.1016/s0301-472x(02)00922-0. View

17.

Jaeger C, Hering B, Hatziagelaki E, Federlin K, Bretzel R . Glutamic acid decarboxylase antibodies are more frequent than islet cell antibodies in islet transplanted IDDM patients and persist or occur despite immunosuppression. J Mol Med (Berl). 1999; 77(1):45-8. DOI: 10.1007/s001090050299. View

18.

Colombo M, Haworth S, Poli F, Nocco A, Puglisi G, Innocente A . Luminex technology for anti-HLA antibody screening: evaluation of performance and of impact on laboratory routine. Cytometry B Clin Cytom. 2007; 72(6):465-71. DOI: 10.1002/cyto.b.20353. View

19.

Amico P, Honger G, Mayr M, Steiger J, Hopfer H, Schaub S . Clinical relevance of pretransplant donor-specific HLA antibodies detected by single-antigen flow-beads. Transplantation. 2009; 87(11):1681-8. DOI: 10.1097/TP.0b013e3181a5e034. View

20.

Campbell P, Senior P, Salam A, LaBranche K, Bigam D, Kneteman N . High risk of sensitization after failed islet transplantation. Am J Transplant. 2007; 7(10):2311-7. DOI: 10.1111/j.1600-6143.2007.01923.x. View