Improved long-term graft function in kidney transplant recipients with donor antigen-specific hyporeactivity.
We investigated the development of donor antigen-specific hyporeactivity by using donor cells as stimulator cells in the MLC and comparing the pre- and post-transplant responses of peripheral blood mononuclear cells. Twenty-two haploidentical pediatric living-relative donor recipients treated with daclizumab, methylprednisone, mofetil mycophenolate and calcineurin inhibitors were tested for study. Of these, 50% of the recipients developed in vitro donor antigen-specific hyporeactivity. The recipients who did so have higher creatinine clearance levels at 12, 24 and 36 months post-transplant (104, 92 and 81 mL/min/1.73 m(2), respectively) than those who remained responsive to donor antigens (77, 74 and 70 mL/min/1.73 m(2)) (p < 0.05). Acute rejection episodes were not observed; however, no recipients with donor-specific hyporeactivity have been diagnosed with CAN, unlike three recipients who remained responsive to donor antigens (0% vs. 27.3%, p = 0.06). Differences in accumulative doses of methylprednisone and mofetil mycophenolate were observed between hyporeactivity- and response-patients to donor antigens at the three years end-point (1.9 +/- 0.8 g/m(2) vs. 4.2 +/- 0.5 g/m(2), and 277 +/- 89 g/m(2) vs. 672 +/- 16.0 g/m(2); p < 0.01 and <0.02, respectively). We conclude that the development of donor antigen-specific hyporeactivity correlate with improved graft function and may permit lower immunosuppression.
Ferraris
Jorge  R
J
Sección Trasplante Renal Pediátrico y Servicio de Histocompatibilidad, Buenos Aires, Argentina. jorge.ferraris@hospitalitaliano.org.ar
Tambutti
Mónica
M
Prigoshin
Norma
N
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D002648:Child; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D000077561:Daclizumab; D009173:Mycophenolic Acid; D008775:Methylprednisolone