Saito Kazuhide, Nakagawa Yuki, Suwa Michihiro, Kumagai Naoki, Tanikawa Toshiki, Nishiyama Tsutomu, Ueno Mitsuhiro, Gejyo Fumitake, Nishi Shin-ichi, Takahashi Kota
Division of Urology, Department of Regenerative and Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Xenotransplantation. 2006 Mar;13(2):111-7. doi: 10.1111/j.1399-3089.2006.00277.x.
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.
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).
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.
Anti-CD20/MMF desensitization is safe and allows successful ABO-I kidney transplantation without splenectomy.
在日本，ABO血型不相容（ABO-I）肾移植始于1989年；由于尸体供体短缺，此类移植手术得以蓬勃发展，截至2004年已实施了600多例。脾切除术被认为是ABO-I肾移植成功的必要条件，在日本，大多数预处理方案都包括脾切除术。然而，尽管患者术前抗体滴度较低，但我们仍有一些移植物因抗A/B抗体（Ab）滴度急剧升高伴发抗体介导的排斥反应（AMR）而丢失。
在ABO-I肾移植中，我们在术前1个月使用两剂抗CD20药物利妥昔单抗，简单地与霉酚酸酯（MMF）/低剂量类固醇脱敏疗法联合使用。通过双重滤过血浆置换或血浆置换进行了两个疗程的术前抗体清除。我们进行了6例不进行脾切除术的ABO-I肾移植。治疗前抗A/B抗体滴度超过16至32倍。我们没有计划任何术后重复抗体清除或静脉注射免疫球蛋白G（IVIG）。
所有病例术前抗A/B抗体滴度均成功降至低于八倍。除1例因吸入性肺炎和耐甲氧西林表皮葡萄球菌（MRSE）败血症而不得不切除移植物外，其他5例均未发生抗体介导的排斥反应（AMR）。无需额外进行术后抗体清除和/或IVIG疗程。在所有患者中，B细胞（CD19+、CD20+、CD21+）和活化T细胞（CD25+）被选择性抑制，尽管CD3+、CD4+和CD8+细胞群体保持稳定，因此我们将我们的方案称为“精准靶向免疫抑制”。血浆免疫球蛋白水平也成功受到抑制，尤其是在术后6周后。
抗CD20/MMF脱敏疗法安全，可在不进行脾切除术的情况下成功进行ABO-I肾移植。
