title: Pharmacodynamics of rituximab in kidney allotransplantation.
abstract: The anti-CD20 antibody rituximab has recently gained interest as a B-cell depleting agent in renal transplantation. However, little is known about the pharmacodynamics of rituximab in renal transplant recipients. We have therefore studied the effect of single-dose rituximab in combination with conventional triple immunosuppressive therapy on the B-cell population in peripheral blood as well as in tissues. A total of 49 renal transplant recipients received single-dose rituximab, as induction therapy (n = 36) or as anti-rejection therapy (n = 13). We counted B cells in peripheral blood and performed immunohistochemical staining on lymph nodes and kidney transplant tissue samples to assess the prevalence of B cells. In all but 6 patients (88%) complete depletion of B cells in peripheral blood was achieved. In adults, 15 months after treatment the CD19+ and CD20+ cell counts were still below 5 cells/muL in the majority of patients (78%). The immunohistochemical staining showed a complete elimination of B cells in kidney tissue and a reduction of B cells in lymph nodes. In conclusion, single-dose rituximab in kidney transplant recipients evokes a long-term elimination of B cells in peripheral blood as well as within the kidney transplant. The effect seems to extend beyond the expected 3-12 months observed in lymphoma patients.
authors.affiliation: Division of Transplantation Surgery, Karolinska Institute Karolinska University Hospital, Huddinge, Sweden. helena.genberg@karolinska.se
authors.forename: H
authors.initials: H
authors.lastname: Genberg
authors.forename: A
authors.initials: A
authors.lastname: Hansson
authors.forename: A
authors.initials: A
authors.lastname: Wernerson
authors.forename: L
authors.initials: L
authors.lastname: Wennberg
authors.forename: G
authors.initials: G
authors.lastname: Tydén
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001706:Biopsy; D002648:Child; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology; D012189:Retrospective Studies; D000069283:Rituximab; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018951:Antigens, CD20; D007155:Immunologic Factors; D000069283:Rituximab