Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal
| Autor: | Hsin-Hsu Wu, Kent P. Jensen, Thomas A. Pham, Philip W. Lavori, John D. Scandling, Marcelo A. Fernandez Viña, Everett Meyer, Jeffrey Waters, Stephan Busque, Kevin Sheehan, Asha Shori, Okmi Choi, Judith A. Shizuru, Robert Lowsky, Richard T. Hoppe, John S. Tamaresis, Samuel Strober, Edgar G. Engleman |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Isoantigens T-Lymphocytes medicine.medical_treatment Naive B cell Human leukocyte antigen 030230 surgery Chimerism Tacrolimus Article Young Adult 03 medical and health sciences 0302 clinical medicine Immune system medicine Humans B cell Kidney transplantation B-Lymphocytes business.industry Histocompatibility Testing Graft Survival General Medicine Middle Aged medicine.disease Kidney Transplantation Survival Analysis Tissue Donors Transplantation Treatment Outcome 030104 developmental biology medicine.anatomical_structure Immunosuppressive drug Haplotypes Withholding Treatment Immunology Female Lymphocyte Culture Test Mixed business Immunosuppressive Agents |
| Zdroj: | Sci Transl Med |
| ISSN: | 1946-6242 1946-6234 |
| Popis: | Preclinical studies have shown that persistent mixed chimerism is linked to acceptance of organ allografts without immunosuppressive (IS) drugs. Mixed chimerism refers to continued mixing of donor and recipient hematopoietic cells in recipient tissues after transplantation of donor cells. To determine whether persistent mixed chimerism and tolerance can be established in patients undergoing living donor kidney transplantation, we infused allograft recipients with donor T cells and hematopoietic progenitors after posttransplant lymphoid irradiation. In 24 of 29 fully human leukocyte antigen (HLA)–matched patients who had persistent mixed chimerism for at least 6 months, complete IS drug withdrawal was achieved without subsequent evidence of rejection for at least 2 years. In 10 of 22 HLA haplotype–matched patients with persistent mixed chimerism for at least 12 months, reduction of IS drugs to tacrolimus monotherapy was achieved. Withdrawal of tacrolimus during the second year resulted in loss of detectable chimerism and subsequent rejection episodes, unless tacrolimus therapy was reinstituted. Posttransplant immune reconstitution of naïve B cells and B cell precursors was more rapid than the reconstitution of naïve T cells and thymic T cell precursors. Robust chimerism was observed only among naïve T and B cells but not among memory T cells. No evidence of rejection was observed in all surveillance graft biopsies obtained from mixed chimeric patients withdrawn from IS drugs, and none developed graft-versus-host disease. In conclusion, persistent mixed chimerism established in fully HLA- or haplotype-matched patients allowed for complete or partial IS drug withdrawal without rejection. |
| Databáze: | OpenAIRE |
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