TY - JOUR
T1 - Sequential Stem Cell-Kidney Transplantation in Schimke Immuno-osseous Dysplasia
AU - Bertaina, Alice
AU - Grimm, Paul C
AU - Weinberg, Kenneth
AU - Parkman, Robertson
AU - Kristovich, Karen M
AU - Barbarito, Giulia
AU - Lippner, Elizabeth
AU - Dhamdhere, Girija
AU - Ramachandran, Vasavi
AU - Spatz, Jordan M
AU - Fathallah-Shaykh, Sahar
AU - Atkinson, T Prescott
AU - Al-Uzri, Amira
AU - Aubert, Geraldine
AU - van der Elst, Kim
AU - Green, Sean G
AU - Agarwal, Rajni
AU - Slepicka, Priscila F
AU - Shah, Ami J
AU - Roncarolo, Maria G
AU - Gallo, Amy
AU - Concepcion, Waldo
AU - Lewis, David B
N1 - Funding Information:
Supported by the Kruzn for a Kure Foundation (to Drs. Ber-taina and Lewis). Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank Dr. Cornelius Boerkoel III (Sanford USD Medical Center and Hospital, Sioux Falls, SD) for useful discussions.
Publisher Copyright:
Copyright © 2022 Massachusetts Medical Society.
PY - 2022/6/16
Y1 - 2022/6/16
N2 - Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. Each patient received sequential transplants of αβ T-cell-depleted and CD19 B-cell-depleted haploidentical hematopoietic stem cells and a kidney from the same donor. Full donor hematopoietic chimerism and functional ex vivo T-cell tolerance was achieved, and the patients continued to have normal renal function without immunosuppression at 22 to 34 months after kidney transplantation.
AB - Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. Each patient received sequential transplants of αβ T-cell-depleted and CD19 B-cell-depleted haploidentical hematopoietic stem cells and a kidney from the same donor. Full donor hematopoietic chimerism and functional ex vivo T-cell tolerance was achieved, and the patients continued to have normal renal function without immunosuppression at 22 to 34 months after kidney transplantation.
KW - Arteriosclerosis/genetics
KW - Graft Rejection/prevention & control
KW - Hematopoietic Stem Cell Transplantation
KW - Humans
KW - Immunologic Deficiency Syndromes/therapy
KW - Kidney Transplantation/adverse effects
KW - Kidney/physiology
KW - Nephrotic Syndrome/genetics
KW - Osteochondrodysplasias/genetics
KW - Primary Immunodeficiency Diseases/genetics
KW - Pulmonary Embolism/genetics
KW - Transplantation Conditioning/methods
UR - https://www.scopus.com/pages/publications/85132131718
U2 - 10.1056/NEJMoa2117028
DO - 10.1056/NEJMoa2117028
M3 - Article
C2 - 35704481
SN - 0028-4793
VL - 386
SP - 2295
EP - 2302
JO - The New England journal of medicine
JF - The New England journal of medicine
IS - 24
ER -