HLA-mismatched renal transplantation without maintenance immunosuppression

Tatsuo Kawai, A. Benedict Cosimi, Thomas R. Spitzer, Nina Tolkoff-Rubin, Manikkam Suthanthiran, Susan L. Saidman, Juanita Shaffer, Frederic I. Preffer, Ruchuang Ding, Vijay Sharma, Jay A. Fishman, Bimalangshu Dey, Dicken S.C. Ko, Martin Hertl, Nelson B. Goes, Waichi Wong, Winfred W. Williams, Robert B. Colvin, Megan Sykes, David H. Sachs

Research output: Contribution to journalArticle

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Abstract

Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA.

Original languageEnglish
Pages (from-to)353-361
Number of pages9
JournalNew England Journal of Medicine
Volume358
Issue number4
DOIs
Publication statusPublished - 24 Jan 2008
Externally publishedYes

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Immunosuppressive Agents
Kidney Transplantation
Immunosuppression
Capillary Leak Syndrome
Maintenance
Granzymes
Messenger RNA
Chimerism
Living Donors
Haplotypes
Chronic Kidney Failure
Allografts
Transplantation
Bone Marrow
Tissue Donors
T-Lymphocytes
Transplants
Kidney
Biopsy
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kawai, T., Cosimi, A. B., Spitzer, T. R., Tolkoff-Rubin, N., Suthanthiran, M., Saidman, S. L., ... Sachs, D. H. (2008). HLA-mismatched renal transplantation without maintenance immunosuppression. New England Journal of Medicine, 358(4), 353-361. https://doi.org/10.1056/NEJMoa071074

HLA-mismatched renal transplantation without maintenance immunosuppression. / Kawai, Tatsuo; Cosimi, A. Benedict; Spitzer, Thomas R.; Tolkoff-Rubin, Nina; Suthanthiran, Manikkam; Saidman, Susan L.; Shaffer, Juanita; Preffer, Frederic I.; Ding, Ruchuang; Sharma, Vijay; Fishman, Jay A.; Dey, Bimalangshu; Ko, Dicken S.C.; Hertl, Martin; Goes, Nelson B.; Wong, Waichi; Williams, Winfred W.; Colvin, Robert B.; Sykes, Megan; Sachs, David H.

In: New England Journal of Medicine, Vol. 358, No. 4, 24.01.2008, p. 353-361.

Research output: Contribution to journalArticle

Kawai, T, Cosimi, AB, Spitzer, TR, Tolkoff-Rubin, N, Suthanthiran, M, Saidman, SL, Shaffer, J, Preffer, FI, Ding, R, Sharma, V, Fishman, JA, Dey, B, Ko, DSC, Hertl, M, Goes, NB, Wong, W, Williams, WW, Colvin, RB, Sykes, M & Sachs, DH 2008, 'HLA-mismatched renal transplantation without maintenance immunosuppression', New England Journal of Medicine, vol. 358, no. 4, pp. 353-361. https://doi.org/10.1056/NEJMoa071074
Kawai, Tatsuo ; Cosimi, A. Benedict ; Spitzer, Thomas R. ; Tolkoff-Rubin, Nina ; Suthanthiran, Manikkam ; Saidman, Susan L. ; Shaffer, Juanita ; Preffer, Frederic I. ; Ding, Ruchuang ; Sharma, Vijay ; Fishman, Jay A. ; Dey, Bimalangshu ; Ko, Dicken S.C. ; Hertl, Martin ; Goes, Nelson B. ; Wong, Waichi ; Williams, Winfred W. ; Colvin, Robert B. ; Sykes, Megan ; Sachs, David H. / HLA-mismatched renal transplantation without maintenance immunosuppression. In: New England Journal of Medicine. 2008 ; Vol. 358, No. 4. pp. 353-361.
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AU - Tolkoff-Rubin, Nina

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AU - Saidman, Susan L.

AU - Shaffer, Juanita

AU - Preffer, Frederic I.

AU - Ding, Ruchuang

AU - Sharma, Vijay

AU - Fishman, Jay A.

AU - Dey, Bimalangshu

AU - Ko, Dicken S.C.

AU - Hertl, Martin

AU - Goes, Nelson B.

AU - Wong, Waichi

AU - Williams, Winfred W.

AU - Colvin, Robert B.

AU - Sykes, Megan

AU - Sachs, David H.

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AB - Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA.

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