A significant role for histocompatibility in human islet transplantation

T. Mohanakumar, Kishore Narayanan, Niraj M Desai, Sabarinathan Ramachandran, Surendra Shenoy, Martin Jendrisak, Brian M. Susskind, Barbara Olack, Nicholas Benshoff, Donna L. Phelan, Daniel Brennan, Luis A. Fernandez, Jon S. Odorico, Kenneth S. Polonsky

Research output: Contribution to journalArticle

Abstract

BACKGROUND. In recent years, transplantation of islets and pancreas has become a viable option for patients debilitated with type I diabetes. The success of islet transplantation has been attributed to the ability to isolate high quality islets for transplantation and capacity to maintain the recipient's immunosuppressive levels within a specific target range following transplantation. The purpose of this study was to determine the role of pretransplant sensitization to human leukocyte antigen (HLA) in islet transplantation. METHODS. We retrospectively analyzed seven patients that were transplanted with islets under the auspices of the Juvenile Diabetes Research Foundation and Islet Cell Resource Center/National Institutes of Health. Humoral sensitization towards donor antigens both prior to and following islet transplantation was detected by FLOW panel reactive antibodies (PRA) and donor-specific cellular sensitization was detected by performing enzyme-linked immunospot assay analysis for cytokines interferon-γ and interleukin-2. RESULTS. Our analysis demonstrates that humoral and cellular sensitization to histocompatibility antigens prior to and after islet transplantation are associated with the failure of transplanted islets CONCLUSION. Patient selection based on sensitization to donor HLA may be one of the factors crucial for the success of islet transplant. Further, in some patients, rejection of islets can be associated with sensitization to mismatched donor histocompatibility antigens.

Original languageEnglish (US)
Pages (from-to)180-187
Number of pages8
JournalTransplantation
Volume82
Issue number2
DOIs
StatePublished - Jul 2006
Externally publishedYes

Fingerprint

Islets of Langerhans Transplantation
Histocompatibility
Histocompatibility Antigens
HLA Antigens
Enzyme-Linked Immunospot Assay
Pancreas Transplantation
National Institutes of Health (U.S.)
Immunosuppressive Agents
Type 1 Diabetes Mellitus
Islets of Langerhans
Interferons
Patient Selection
Interleukin-2
Transplantation
Tissue Donors
Cytokines
Transplants
Antigens
Antibodies
Research

Keywords

  • Antibody
  • Histocompatibility
  • Islets
  • Transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Mohanakumar, T., Narayanan, K., Desai, N. M., Ramachandran, S., Shenoy, S., Jendrisak, M., ... Polonsky, K. S. (2006). A significant role for histocompatibility in human islet transplantation. Transplantation, 82(2), 180-187. https://doi.org/10.1097/01.tp.0000226161.82581.b2

A significant role for histocompatibility in human islet transplantation. / Mohanakumar, T.; Narayanan, Kishore; Desai, Niraj M; Ramachandran, Sabarinathan; Shenoy, Surendra; Jendrisak, Martin; Susskind, Brian M.; Olack, Barbara; Benshoff, Nicholas; Phelan, Donna L.; Brennan, Daniel; Fernandez, Luis A.; Odorico, Jon S.; Polonsky, Kenneth S.

In: Transplantation, Vol. 82, No. 2, 07.2006, p. 180-187.

Research output: Contribution to journalArticle

Mohanakumar, T, Narayanan, K, Desai, NM, Ramachandran, S, Shenoy, S, Jendrisak, M, Susskind, BM, Olack, B, Benshoff, N, Phelan, DL, Brennan, D, Fernandez, LA, Odorico, JS & Polonsky, KS 2006, 'A significant role for histocompatibility in human islet transplantation', Transplantation, vol. 82, no. 2, pp. 180-187. https://doi.org/10.1097/01.tp.0000226161.82581.b2
Mohanakumar T, Narayanan K, Desai NM, Ramachandran S, Shenoy S, Jendrisak M et al. A significant role for histocompatibility in human islet transplantation. Transplantation. 2006 Jul;82(2):180-187. https://doi.org/10.1097/01.tp.0000226161.82581.b2
Mohanakumar, T. ; Narayanan, Kishore ; Desai, Niraj M ; Ramachandran, Sabarinathan ; Shenoy, Surendra ; Jendrisak, Martin ; Susskind, Brian M. ; Olack, Barbara ; Benshoff, Nicholas ; Phelan, Donna L. ; Brennan, Daniel ; Fernandez, Luis A. ; Odorico, Jon S. ; Polonsky, Kenneth S. / A significant role for histocompatibility in human islet transplantation. In: Transplantation. 2006 ; Vol. 82, No. 2. pp. 180-187.
@article{d295331914f0476bad9de8de14c62624,
title = "A significant role for histocompatibility in human islet transplantation",
abstract = "BACKGROUND. In recent years, transplantation of islets and pancreas has become a viable option for patients debilitated with type I diabetes. The success of islet transplantation has been attributed to the ability to isolate high quality islets for transplantation and capacity to maintain the recipient's immunosuppressive levels within a specific target range following transplantation. The purpose of this study was to determine the role of pretransplant sensitization to human leukocyte antigen (HLA) in islet transplantation. METHODS. We retrospectively analyzed seven patients that were transplanted with islets under the auspices of the Juvenile Diabetes Research Foundation and Islet Cell Resource Center/National Institutes of Health. Humoral sensitization towards donor antigens both prior to and following islet transplantation was detected by FLOW panel reactive antibodies (PRA) and donor-specific cellular sensitization was detected by performing enzyme-linked immunospot assay analysis for cytokines interferon-γ and interleukin-2. RESULTS. Our analysis demonstrates that humoral and cellular sensitization to histocompatibility antigens prior to and after islet transplantation are associated with the failure of transplanted islets CONCLUSION. Patient selection based on sensitization to donor HLA may be one of the factors crucial for the success of islet transplant. Further, in some patients, rejection of islets can be associated with sensitization to mismatched donor histocompatibility antigens.",
keywords = "Antibody, Histocompatibility, Islets, Transplantation",
author = "T. Mohanakumar and Kishore Narayanan and Desai, {Niraj M} and Sabarinathan Ramachandran and Surendra Shenoy and Martin Jendrisak and Susskind, {Brian M.} and Barbara Olack and Nicholas Benshoff and Phelan, {Donna L.} and Daniel Brennan and Fernandez, {Luis A.} and Odorico, {Jon S.} and Polonsky, {Kenneth S.}",
year = "2006",
month = "7",
doi = "10.1097/01.tp.0000226161.82581.b2",
language = "English (US)",
volume = "82",
pages = "180--187",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - A significant role for histocompatibility in human islet transplantation

AU - Mohanakumar, T.

AU - Narayanan, Kishore

AU - Desai, Niraj M

AU - Ramachandran, Sabarinathan

AU - Shenoy, Surendra

AU - Jendrisak, Martin

AU - Susskind, Brian M.

AU - Olack, Barbara

AU - Benshoff, Nicholas

AU - Phelan, Donna L.

AU - Brennan, Daniel

AU - Fernandez, Luis A.

AU - Odorico, Jon S.

AU - Polonsky, Kenneth S.

PY - 2006/7

Y1 - 2006/7

N2 - BACKGROUND. In recent years, transplantation of islets and pancreas has become a viable option for patients debilitated with type I diabetes. The success of islet transplantation has been attributed to the ability to isolate high quality islets for transplantation and capacity to maintain the recipient's immunosuppressive levels within a specific target range following transplantation. The purpose of this study was to determine the role of pretransplant sensitization to human leukocyte antigen (HLA) in islet transplantation. METHODS. We retrospectively analyzed seven patients that were transplanted with islets under the auspices of the Juvenile Diabetes Research Foundation and Islet Cell Resource Center/National Institutes of Health. Humoral sensitization towards donor antigens both prior to and following islet transplantation was detected by FLOW panel reactive antibodies (PRA) and donor-specific cellular sensitization was detected by performing enzyme-linked immunospot assay analysis for cytokines interferon-γ and interleukin-2. RESULTS. Our analysis demonstrates that humoral and cellular sensitization to histocompatibility antigens prior to and after islet transplantation are associated with the failure of transplanted islets CONCLUSION. Patient selection based on sensitization to donor HLA may be one of the factors crucial for the success of islet transplant. Further, in some patients, rejection of islets can be associated with sensitization to mismatched donor histocompatibility antigens.

AB - BACKGROUND. In recent years, transplantation of islets and pancreas has become a viable option for patients debilitated with type I diabetes. The success of islet transplantation has been attributed to the ability to isolate high quality islets for transplantation and capacity to maintain the recipient's immunosuppressive levels within a specific target range following transplantation. The purpose of this study was to determine the role of pretransplant sensitization to human leukocyte antigen (HLA) in islet transplantation. METHODS. We retrospectively analyzed seven patients that were transplanted with islets under the auspices of the Juvenile Diabetes Research Foundation and Islet Cell Resource Center/National Institutes of Health. Humoral sensitization towards donor antigens both prior to and following islet transplantation was detected by FLOW panel reactive antibodies (PRA) and donor-specific cellular sensitization was detected by performing enzyme-linked immunospot assay analysis for cytokines interferon-γ and interleukin-2. RESULTS. Our analysis demonstrates that humoral and cellular sensitization to histocompatibility antigens prior to and after islet transplantation are associated with the failure of transplanted islets CONCLUSION. Patient selection based on sensitization to donor HLA may be one of the factors crucial for the success of islet transplant. Further, in some patients, rejection of islets can be associated with sensitization to mismatched donor histocompatibility antigens.

KW - Antibody

KW - Histocompatibility

KW - Islets

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=33746447618&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746447618&partnerID=8YFLogxK

U2 - 10.1097/01.tp.0000226161.82581.b2

DO - 10.1097/01.tp.0000226161.82581.b2

M3 - Article

C2 - 16858280

AN - SCOPUS:33746447618

VL - 82

SP - 180

EP - 187

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 2

ER -