HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression
Tatsuo Kawai, M.D., A. Benedict Cosimi, M.D., Thomas R. Spitzer, M.D., Nina Tolkoff-Rubin, M.D., Manikkam Suthanthiran, M.D., Susan L. Saidman, Ph.D., Juanita Shaffer, B.S., Frederic I. Preffer, Ph.D., Ruchuang Ding, M.D., Vijay Sharma, Ph.D., Jay A. Fishman, M.D., Bimalangshu Dey, M.D., Dicken S.C. Ko, M.D., Martin Hertl, M.D., Nelson B. Goes, M.D., Waichi Wong, M.D., Winfred W. Williams, Jr., M.D., Robert B. Colvin, M.D., Megan Sykes, M.D., and David H. Sachs, M.D.
Five patients with end-stage renal disease received combinedbone marrow and kidney transplants from HLA single-haplotypemismatched living related donors, with the use of a nonmyeloablativepreparative regimen. Transient chimerism and reversible capillaryleak syndrome developed in all recipients. Irreversible humoralrejection occurred in one patient. In the other four recipients,it was possible to discontinue all immunosuppressive therapy9 to 14 months after the transplantation, and renal functionhas remained stable for 2.0 to 5.3 years since transplantation.The T cells from these four recipients, tested in vitro, showeddonor-specific unresponsiveness and in specimens from allograftbiopsies, obtained after withdrawal of immunosuppressive therapy,there were high levels of P3 (FOXP3) messenger RNA (mRNA) butnot granzyme B mRNA.
Source Information
From the Transplantation Unit (T.K., A.B.C., N.T.-R., J.A.F., D.S.C.K., M.H., N.B.G., W.W., W.W.W.), Transplantation Biology Research Center (J.S., M. Sykes, D.H.S.), Bone Marrow Transplantation Program, Department of Medicine (T.R.S., B.D.), and Department of Pathology (S.L.S., F.I.P., R.B.C.), Massachusetts General Hospital, and Harvard Medical School, Boston; and the Division of Nephrology, Department of Medicine and Transplant Medicine, New York Presbyterian Hospital–Weill Cornell Medical Center, New York (M. Suthanthiran, R.D., V.S.).
Address reprint requests to Dr. Sachs at Massachusetts General Hospital Transplantation Biology Research Center, 149 13th St., Charlestown, MA 02129.
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