Immune Profile of Pediatric Renal Transplant Recipients following Alemtuzumab Induction

• Published in: Journal of the American Society of Nephrology 2012-01, Vol.23 (1), p.174-182
• Main Authors: DE SERRES, Sacha A, MFARREJ, Bechara G, MAGEE, Ciara N, BENITEZ, Fanny, ASHOOR, Isa, SAYEGH, Mohamed H, HARMON, William E, NAJAFIAN, Nader
• Format: Article
• Language: English
• Subjects: Adolescent; Alemtuzumab; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Neoplasm - pharmacology; Antineoplastic Agents - pharmacology; Biological and medical sciences; Child; Clinical Research; Female; HLA Antigens - immunology; Humans; Immunosuppression; Kidney Transplantation - immunology; Male; Medical sciences; Nephrology. Urinary tract diseases; Prospective Studies; T-Lymphocytes - drug effects
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2011040360

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.