title: Immune profile of pediatric renal transplant recipients following alemtuzumab induction.
abstract: The incidence of developing circulating anti-human leukocyte antigen antibodies and the kinetics of T cell depletion and recovery among pediatric renal transplant recipients who receive alemtuzumab induction therapy are unknown. In a collaborative endeavor to minimize maintenance immunosuppression in pediatric renal transplant recipients, we enrolled 35 participants from four centers and treated them with alemtuzumab induction therapy and a steroid-free, calcineurin-inhibitor-withdrawal maintenance regimen. At 3 months after transplant, there was greater depletion of CD4(+) than CD8(+) T cells within the total, naive, memory, and effector memory subsets, although depletion of the central memory subset was similar for CD4(+) and CD8(+) cells. Although CD8(+) T cells recovered faster than CD4(+) subsets overall, they failed to return to pretransplant levels by 24 months after transplant. There was no evidence for greater recovery of either CD4(+) or CD8(+) memory cells than naïve cells. Alemtuzumab relatively spared CD4(+)CD25(+)FoxP3(+) regulatory T cells, resulting in a rise in their numbers relative to total CD4(+) cells and a ratio that remained at least at pretransplant levels throughout the study period. Seven participants (20%) developed anti-human leukocyte antigen antibodies without adversely affecting allograft function or histology on 2-year biopsies. Long-term follow-up is underway to assess the potential benefits of this regimen in children.
authors: Brigham and Women's Hospital, Transplantation Research Center, 221 Longwood Ave, 3rd Floor, Boston, MA 02115, USA.
authors: Sacha A
authors: SA
authors: De Serres
authors: Bechara G
authors: BG
authors: Mfarrej
authors: Ciara N
authors: CN
authors: Magee
authors: Fanny
authors: F
authors: Benitez
authors: Isa
authors: I
authors: Ashoor
authors: Mohamed H
authors: MH
authors: Sayegh
authors: William E
authors: WE
authors: Harmon
authors: Nader
authors: N
authors: Najafian
mesh_terms: D000293:Adolescent; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002648:Child; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D006680:HLA Antigens; D000074323:Alemtuzumab