Pharmacodynamics of rituximab in kidney transplantation.
The B-cell depleting anti-CD20 antibody rituximab has become a therapeutic alternative in renal transplantation. However, understanding of the pharmacodynamics is limited. 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, in kidney transplant recipients. Forty-nine kidney recipients received single-dose rituximab. The prevalence of B cells was assessed in peripheral blood, kidney transplant tissue, and in lymph nodes. In 88%, complete depletion of B cells in peripheral blood was observed and, 15 months after treatment, B cells were still undetectable in the majority of patients. In kidney tissue, B cells were also completely eliminated. In contrast, the B cells were not eliminated in lymph nodes, although a reduction was observed. 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.
Genberg
Helena
H
Department of Transplantation Surgery, Karolinska University Hospital, Huddinge, Sweden. helena.genberg@karolinska.se
Hansson
Anneli
A
Wernerson
Annika
A
Wennberg
Lars
L
Tydén
Gunnar
G
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000096:biosynthesis; D018951:Antigens, CD20 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000378:metabolism; D002648:Child; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D008198:Lymph Nodes / Q000473:pathology; D008954:Models, Biological; D000069283:Rituximab; D014181:Transplantation Immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018951:Antigens, CD20; D007166:Immunosuppressive Agents; D000069283:Rituximab