Pinpoint targeted immunosuppression: anti-CD20/MMF desensitization with anti-CD25 in successful ABO-incompatible kidney transplantation without splenectomy.
BACKGROUND
In Japan, ABO-incompatible (ABO-I) kidney transplantation began in 1989; these transplantations have flourished because of the lack of cadaveric donors, and more than 600 cases were performed up to 2004. Splenectomy has been considered to be necessary for successful ABO-I kidney transplantation, and the majority of pre-conditioning protocols include splenectomy in Japan. However, we have lost some grafts due to antibody-mediated rejection (AMR) accompanying explosive elevation of anti-A/B antibody (Ab) titer even though the patients had a low pre-operative Ab titer.


METHODS
We utilized two doses of anti-CD20, rituximab, simply combined with mycophenolate mofetil (MMF)/low-dose steroid desensitization started 1 month before surgery in ABO-I kidney transplantation. Two sessions of pre-operative Ab removal by double filtration plasmapheresis or plasma exchange were carried out. We performed six ABO-I kidney transplantations without splenectomy. Anti-A/B Ab titers were more than 16 to 32 times before treatment. We did not plan any post-operative repeated Ab removal or intravenous immunoglobulin G (IVIG).


RESULTS
Pre-operative anti-A/B Ab titers were successfully reduced to less than eight times in all cases. Except for one case in which we had to remove the graft due to aspiration pneumonia and methicillin-resistant staphylococcus epidermidis (MRSE) sepsis, the other five cases did not experience antibody-mediated rejection (AMR). An additional session of post-operative Ab removal and/or IVIG was not necessary. In all patients, B cells (CD19+, CD20+, CD21+) and activated T cells (CD25+) were selectively suppressed, although CD3+, CD4+ and CD8+ cell populations remained stable, thus we call our protocol "pinpoint targeted immunosuppression." Plasma immunoglobulin level was also successfully suppressed, especially after 6 weeks of surgery.


CONCLUSIONS
Anti-CD20/MMF desensitization is safe and allows successful ABO-I kidney transplantation without splenectomy.
Saito
Kazuhide
K
Division of Urology, Department of Regenerative and Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan. kazsaito@med.niigata-u.ac.jp
Nakagawa
Yuki
Y
Suwa
Michihiro
M
Kumagai
Naoki
N
Tanikawa
Toshiki
T
Nishiyama
Tsutomu
T
Ueno
Mitsuhiro
M
Gejyo
Fumitake
F
Nishi
Shin-ichi
S
Takahashi
Kota
K
D000017:ABO Blood-Group System / Q000276:immunology*; D000208:Acute Disease; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D000077552:Basiliximab; D001787:Blood Group Incompatibility / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D000069283:Rituximab; D013156:Splenectomy; D016896:Treatment Outcome
D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D000069283:Rituximab; D000077552:Basiliximab; D009173:Mycophenolic Acid