Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes

M. D. Bellin, F. B. Barton, A. Heitman, J. V. Harmon, R. Kandaswamy, A. N. Balamurugan, D. E R Sutherland, Rodolfo Alejandro, B. J. Hering

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

The seemingly inexorable decline in insulin independence after islet transplant alone (ITA) has raised concern about its clinical utility. We hypothesized that induction immunosuppression therapy determines durability of insulin independence. We analyzed the proportion of insulin-independent patients following final islet infusion in four groups of ITA recipients according to induction immunotherapy: University of Minnesota recipients given FcR nonbinding anti-CD3 antibody alone or T cell depleting antibodies (TCDAb) and TNF-α inhibition (TNF-α-i) (group 1; n = 29); recipients reported to the Collaborative Islet Transplant Registry (CITR) given TCDAb+TNF-α-i (group 2; n = 20); CITR recipients given TCDAb without TNF-α-i (group 3; n = 43); and CITR recipients given IL-2 receptor antibodies (IL-2RAb) alone (group 4; n = 177). Results were compared with outcomes in pancreas transplant alone (PTA) recipients reported to the Scientific Registry of Transplant Recipients (group 5; n = 677). The 5-year insulin independence rates in group 1 (50%) and group 2 (50%) were comparable to outcomes in PTA (group 5: 52%; p>>0.05) but significantly higher than in group 3 (0%; p = 0.001) and group 4 (20%; p = 0.02). Induction immunosuppression was significantly associated with 5-year insulin independence (p = 0.03), regardless of maintenance immunosuppression or other factors. These findings support potential for long-term insulin independence after ITA using potent induction therapy, with anti-CD3 Ab or TCDAb+TNF-α-i. Islet transplant recipients who receive induction immunosuppression with one of several depletional antibody preparations are more likely to exhibit long-term insulin independence at 3 and 5 years posttransplant than patients who do not receive depletional induction therapy based on data from the Collaborative Islet Transplant Registry.

Original languageEnglish
Pages (from-to)1576-1583
Number of pages8
JournalAmerican Journal of Transplantation
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2012

Fingerprint

Islets of Langerhans Transplantation
Type 1 Diabetes Mellitus
Immunotherapy
Insulin
Registries
Immunosuppression
Antibodies
Transplants
T-Lymphocytes
Pancreas
Interleukin-2 Receptors
Transplant Recipients
Anti-Idiotypic Antibodies
Therapeutics
Maintenance

Keywords

  • Alemtuzumab
  • antithymocyte globulin
  • CD3
  • islet transplant
  • OKT3
  • T cell

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Bellin, M. D., Barton, F. B., Heitman, A., Harmon, J. V., Kandaswamy, R., Balamurugan, A. N., ... Hering, B. J. (2012). Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes. American Journal of Transplantation, 12(6), 1576-1583. https://doi.org/10.1111/j.1600-6143.2011.03977.x

Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes. / Bellin, M. D.; Barton, F. B.; Heitman, A.; Harmon, J. V.; Kandaswamy, R.; Balamurugan, A. N.; Sutherland, D. E R; Alejandro, Rodolfo; Hering, B. J.

In: American Journal of Transplantation, Vol. 12, No. 6, 01.06.2012, p. 1576-1583.

Research output: Contribution to journalArticle

Bellin, MD, Barton, FB, Heitman, A, Harmon, JV, Kandaswamy, R, Balamurugan, AN, Sutherland, DER, Alejandro, R & Hering, BJ 2012, 'Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes', American Journal of Transplantation, vol. 12, no. 6, pp. 1576-1583. https://doi.org/10.1111/j.1600-6143.2011.03977.x
Bellin, M. D. ; Barton, F. B. ; Heitman, A. ; Harmon, J. V. ; Kandaswamy, R. ; Balamurugan, A. N. ; Sutherland, D. E R ; Alejandro, Rodolfo ; Hering, B. J. / Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes. In: American Journal of Transplantation. 2012 ; Vol. 12, No. 6. pp. 1576-1583.
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abstract = "The seemingly inexorable decline in insulin independence after islet transplant alone (ITA) has raised concern about its clinical utility. We hypothesized that induction immunosuppression therapy determines durability of insulin independence. We analyzed the proportion of insulin-independent patients following final islet infusion in four groups of ITA recipients according to induction immunotherapy: University of Minnesota recipients given FcR nonbinding anti-CD3 antibody alone or T cell depleting antibodies (TCDAb) and TNF-α inhibition (TNF-α-i) (group 1; n = 29); recipients reported to the Collaborative Islet Transplant Registry (CITR) given TCDAb+TNF-α-i (group 2; n = 20); CITR recipients given TCDAb without TNF-α-i (group 3; n = 43); and CITR recipients given IL-2 receptor antibodies (IL-2RAb) alone (group 4; n = 177). Results were compared with outcomes in pancreas transplant alone (PTA) recipients reported to the Scientific Registry of Transplant Recipients (group 5; n = 677). The 5-year insulin independence rates in group 1 (50{\%}) and group 2 (50{\%}) were comparable to outcomes in PTA (group 5: 52{\%}; p>>0.05) but significantly higher than in group 3 (0{\%}; p = 0.001) and group 4 (20{\%}; p = 0.02). Induction immunosuppression was significantly associated with 5-year insulin independence (p = 0.03), regardless of maintenance immunosuppression or other factors. These findings support potential for long-term insulin independence after ITA using potent induction therapy, with anti-CD3 Ab or TCDAb+TNF-α-i. Islet transplant recipients who receive induction immunosuppression with one of several depletional antibody preparations are more likely to exhibit long-term insulin independence at 3 and 5 years posttransplant than patients who do not receive depletional induction therapy based on data from the Collaborative Islet Transplant Registry.",
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