Failure of Anti-CD20 Monoclonal Antibody Therapy to Prevent Antibody-Mediated Rejection in Three Crossmatch-Positive Renal Transplant Recipients

• Published in: Transplantation proceedings Vol. 39; no. 8; pp. 2565 - 2567
• Main Authors: Matignon, M., Tagnaouti, M., Audard, V., Dahan, K., Lang, P., Grimbert, P.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2007; Elsevier Science
• Subjects: Adult; Antibodies, Monoclonal - therapeutic use; Antigens, CD - immunology; Antigens, CD20 - immunology; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - immunology; Histocompatibility Testing; Humans; Kidney Transplantation - immunology; Male; Medical sciences; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Treatment Failure; Graft(material); Transplantation; Monoclonal antibody; Homotransplantation; Kidney; Medicine; Prevention; Rejection; Treatment; Urinary system; Surgery; Immunotherapy; Graft; Failure
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2007.08.038

There is no optimal desensitization protocol for cadaveric renal transplant recipients who display high levels of donor-specific alloantibodies as defined by a positive T- or B-cell cytotoxic crossmatch. We used anti-CD20 monoclonal antibodies (Rituximab) to try to prevent antibody-mediated rejection in three crossmatch-positive renal transplants recipients (standard and sensitized techniques). The three patients received a first, second, or third cadaveric donor renal transplant. Patient one had an historical positive T- and B-cell cytotoxicity crossmatch: negative T- and B-cell cytotoxicity crossmatch at the day of transplantation. The panel reactive antibody (PRA) level was 100%. Patients 2 and 3 showed positive B-cell cytotoxicity crossmatches: historical and on the day of transplantation; PRA levels were 50% and 71%, respectively. All recipients were treated pretransplant with rituximab (375 mg/m 2) and 4 days of intravenous immunoglobulin (0.5 g/kg body weight) per day posttransplant plus 5 days of thymoglobulin. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and prednisone. Antibody-mediated rejection occured in all patients at day 6, day 10, or 8 months after renal transplantation. For patient 1, the rejection was not reversible and the graft was lost at day 15. Patient 2 had poor renal function with an MDRD estimate of glomerular filtration rate at 36 mL/min/1.73 m 2 at 18 months posttransplantation, and the graft of patient 3 was lost at 9 months posttransplantation due to resistant antibody-mediated rejection with thrombotic microangiopathy. In these three cases of crossmatch-positive patients, rituximab failed to prevent antibody-mediated rejection. Others studies will be needed to determine the place of rituximab in these patients.