B‐cell surface marker analysis for improvement of rituximab prophylaxis in ABO‐incompatible adult living donor liver transplantation

• Published in: Liver transplantation Vol. 13; no. 4; pp. 579 - 588
• Main Authors: Egawa, Hiroto, Ohmori, Katsuyuki, Haga, Hironori, Tsuji, Hiroaki, Yurugi, Kimiko, Miyagawa‐Hayashino, Aya, Oike, Fumitaka, Fukuda, Akinari, Yoshizawa, Jun, Takada, Yasutsugu, Tanaka, Koichi, Maekawa, Taira, Ozawa, Kazue, Uemoto, Shinji
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2007
• Subjects: ABO Blood-Group System; Adolescent; Adult; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Murine-Derived; B-Lymphocytes - immunology; Biomarkers - analysis; Blood Group Incompatibility; Female; Humans; Immunologic Factors - therapeutic use; Immunosuppression; Liver Transplantation - immunology; Living Donors; Lymph Nodes - immunology; Male; Rituximab; Splenectomy
• ISSN: 1527-6465; 1527-6473
• DOI: 10.1002/lt.21092

Although the effectiveness of rituximab has been reported in ABO blood group (ABO)‐incompatible (ABO‐I) organ transplantation, the protocol is not yet established. We studied the impact of the timing of rituximab prophylaxis and the humoral immune response of patients undergoing ABO‐I living donor liver transplantation (LDLT), focusing on clinicopathological findings and the B‐cell subset. From July 2003 to December 2005, 30 adult patients were treated with hepatic artery infusion (HAI) protocol without splenectomy for ABO‐I LDLT. A total of 17 patients were treated only with HAI (no prophylaxis), and the other 13 were treated with rituximab prophylaxis at various times prior to transplantation. For B‐cell study of the spleen, another 4 patients undergoing ABO‐I LDLT both with HAI after prophylaxis and eventual splenectomy, and 3 patients with ABO‐compatible LDLT with splenectomy were enrolled. The mortality of the 30 patients with HAI, without splenectomy, and with/without rituximab prophylaxis was 33% and the main cause of death was sepsis. Peripheral blood B cells were completely depleted, anti‐donor blood‐type antibody titer was lower, and clinical and pathological antibody‐mediated rejection was not observed in patients with prophylaxis earlier than 7 days before transplantation (early prophylaxis). Early rituximab prophylaxis significantly depleted B cells and memory B cells in the spleen but not in lymph nodes. On the other hand, B cells and memory B cells increased and memory B cells became dominant during antibody‐mediated rejection. In conclusion, early prophylaxis with rituximab depletes B cells, including memory B cells, in the spleen and is associated with a trend toward lower humoral rejection rates and lower peak immunoglobulin (Ig)G titers in ABO‐I LDLT patients. Liver Transpl 13:579–588, 2007. © 2007 AASLD.