B-cell surface marker analysis for improvement of rituximab prophylaxis in ABO-incompatible adult living donor liver transplantation.
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.
Egawa
Hiroto
H
Department of Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan. egawa@kuhp.kyoto-u.ac.jp
Ohmori
Katsuyuki
K
Haga
Hironori
H
Tsuji
Hiroaki
H
Yurugi
Kimiko
K
Miyagawa-Hayashino
Aya
A
Oike
Fumitaka
F
Fukuda
Akinari
A
Yoshizawa
Jun
J
Takada
Yasutsugu
Y
Tanaka
Koichi
K
Maekawa
Taira
T
Ozawa
Kazue
K
Uemoto
Shinji
S
D000017:ABO Blood-Group System; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D001787:Blood Group Incompatibility; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007165:Immunosuppression Therapy; D016031:Liver Transplantation / Q000276:immunology*; D019520:Living Donors; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D000069283:Rituximab; D013156:Splenectomy
D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; D007155:Immunologic Factors; D000069283:Rituximab