Reconstitution of peripheral allospecific CD19+ B-cell subsets after B-lymphocyte depletion therapy in renal transplant patients. Export

@article{citeulike:5908858, abstract = {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.}, author = {Kopchaliiska, Dessislava and Zachary, Andrea A. and Montgomery, Robert A. and Leffell, Mary S.}, citeulike-article-id = {5908858}, citeulike-linkout-0 = {http://dx.doi.org/10.1097/TP.0b013e3181a27683}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19424042}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19424042}, day = {15}, doi = {10.1097/TP.0b013e3181a27683}, issn = {1534-6080}, journal = {Transplantation}, keywords = {b-cell, cd19, memory, renal, transplantation}, month = {May}, number = {9}, pages = {1394--1401}, posted-at = {2009-10-08 09:41:08}, priority = {2}, title = {Reconstitution of peripheral allospecific CD19+ B-cell subsets after B-lymphocyte depletion therapy in renal transplant patients.}, url = {http://dx.doi.org/10.1097/TP.0b013e3181a27683}, volume = {87}, year = {2009} }

TY - JOUR ID - citeulike:5908858 L3 - citeulike-article-id:5908858 N2 - 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. IS - 9 JF - Transplantation SN - 1534-6080 EP - 1401 TI - Reconstitution of peripheral allospecific CD19+ B-cell subsets after B-lymphocyte depletion therapy in renal transplant patients. VL - 87 SP - 1394 KW - b-cell KW - cd19 KW - memory KW - renal KW - transplantation AU - Kopchaliiska, Dessislava AU - Zachary, Andrea AU - Montgomery, Robert AU - Leffell, Mary PY - 2009/05/15/ UR - http://dx.doi.org/10.1097/TP.0b013e3181a27683 ER -