PMID- 19424042 OWN - NLM STAT- MEDLINE DCOM- 20090708 LR - 20090508 IS - 1534-6080 (Electronic) IS - 0041-1337 (Linking) VI - 87 IP - 9 DP - 2009 May 15 TI - Reconstitution of peripheral allospecific CD19+ B-cell subsets after B-lymphocyte depletion therapy in renal transplant patients. PG - 1394-401 LID - 10.1097/TP.0b013e3181a27683 [doi] AB - BACKGROUND: Desensitization protocols, which frequently use lymphocyte depleting agents have increased access to successful transplantation for sensitized candidates. Here, we report on the reconstitution of human leukocyte antigen (HLA)-specific B lymphocytes in renal transplant patients after treatment with B-lymphocyte depletion. METHODS: Sixteen renal transplant candidates were included in the study. Eleven patients were treated with anti-CD20 monoclonal antibody (Ab), four of whom also underwent splenectomy perioperatively. Five patients who did not undergo B-cell depletion were studied as controls. Blood samples were obtained before any treatment and transplant, and at later time points up to 44 months posttransplant. HLA-specific B-cell subpopulations were identified by staining with fluorochrome-labeled HLA tetramers and anti-CD19, CD27, and CD38 monoclonal Abs. RESULTS: Total circulating B lymphocytes repopulated within 12 months post-B-cell depletion. The majority of the recovering cells had the phenotype of transitional CD38 B cells and the percentages of mature, memory CD27 B cells remained significantly depressed. There was a sustained reduction in the proportion of HLA-specific CD27 memory B cells, whereas the HLA-specific CD38 B-cell population returned to near pretreatment levels by 12 months. The presence of mismatched HLA antigens seemed to affect the reconstitution kinetics. The delay in reconstitution of HLA-specific CD27 memory B cells was greater for donor-specific compared with third party. CONCLUSIONS: A delay in functional maturity of repopulating HLA-specific B cells, and in particular those specific for donor HLA, after B-lymphocyte depletion treatment in renal transplant recipients may contribute to the efficacy of desensitization protocols. FAU - Kopchaliiska, Dessislava AU - Kopchaliiska D AD - Department of Medicine, Immunogenetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. dkopchal@jhmi.edu FAU - Zachary, Andrea A AU - Zachary AA FAU - Montgomery, Robert A AU - Montgomery RA FAU - Leffell, Mary S AU - Leffell MS LA - eng PT - Journal Article PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (Antigens, CD19) RN - 0 (HLA Antigens) SB - IM MH - Antibodies, Monoclonal/therapeutic use MH - Antigens, CD MH - Antigens, CD19/*immunology MH - B-Lymphocyte Subsets/*immunology/transplantation MH - Female MH - HLA Antigens/immunology MH - Humans MH - Kidney Transplantation/*immunology MH - Lymphocyte Depletion/*adverse effects MH - *Lymphocyte Transfusion MH - Male MH - Splenectomy MH - Transplantation, Homologous/immunology EDAT- 2009/05/09 09:00 MHDA- 2009/07/09 09:00 CRDT- 2009/05/09 09:00 PHST- 2009/05/09 09:00 [entrez] PHST- 2009/05/09 09:00 [pubmed] PHST- 2009/07/09 09:00 [medline] AID - 00007890-200905150-00021 [pii] AID - 10.1097/TP.0b013e3181a27683 [doi] PST - ppublish SO - Transplantation. 2009 May 15;87(9):1394-401. doi: 10.1097/TP.0b013e3181a27683.