Ishida Hideki, Tanabe Kazunari, Furusawa Miyuki, Ishizuka Tsutomu, Shimmura Hiroaki, Tokumoto Tadahiko, Hayashi Tetsuo, Toma Hiroshi
Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan.
Transplantation. 2002 Oct 27;74(8):1187-9. doi: 10.1097/00007890-200210270-00023.
The introduction of novel immunosuppressive drugs has made it possible to achieve dramatic improvement in graft survival rates. In particular, the current immunosuppressive regimen including mycophenolate mofetil (MMF) has yielded excellent results including a nearly 100% 1-year graft survival rate at our institution in 2001. We used enzyme-linked immunosorbent assay (ELISA) to analyze humoral activity after ABO-mismatched renal transplantation using the MMF regimen.
The patient received an ABO-mismatched graft from a living related sibling. Preoperatively, he underwent plasma exchange (PEX) and double-filtration plasmapheresis (DFPP) several times to remove anti-blood type antibodies. Mycophenolate mofetil was used as one of the induction regimens, but a switch was made to other drugs because of persistent gastrointestinal tract discomfort. Mycophenolate mofetil was restarted, however, because of graft dysfunction caused by severe humoral rejection. Humoral activity in this patient was investigated by ELISA during the postoperative follow-up.
Anti-blood type antibody immunoglobulin (Ig) M and IgG decreased immediately before the operation because of repeated PEX and DFPP. Both IgM and IgG were postoperatively stable and graft function was excellent. However, after switching from MMF to mizoribine (MZ), renal graft function gradually deteriorated, and the deterioration was associated with elevation of anti-blood type antibody, predominantly IgG. IgM antibody production was parallel to that of IgG, but was weaker. The elevated activity of anti-blood type antibody IgG decreased to the normal level as renal function recovered after MMF was restarted.
Anti-blood type antibody IgG decreased after the administration of MMF after ABO-mismatched renal transplantation, and it increased after withdrawal of MMF. MMF seems to affect B-cell populations that produce anti-blood type antibodies after renal transplantation across the blood barrier.
新型免疫抑制药物的引入使移植存活率得到显著提高。特别是,目前包括霉酚酸酯(MMF)在内的免疫抑制方案取得了优异的效果,2001年在我们机构1年移植存活率接近100%。我们采用酶联免疫吸附测定(ELISA)分析了使用MMF方案进行ABO血型不相容肾移植后的体液活性。
该患者接受了来自活体亲属的ABO血型不相容移植肾。术前,他多次接受血浆置换(PEX)和双重滤过血浆置换(DFPP)以清除抗血型抗体。霉酚酸酯被用作诱导方案之一,但由于持续的胃肠道不适而改用其他药物。然而,由于严重体液排斥导致移植肾功能障碍,又重新启用了霉酚酸酯。在术后随访期间通过ELISA研究了该患者的体液活性。
由于反复进行PEX和DFPP,术前抗血型抗体免疫球蛋白(Ig)M和IgG立即下降。术后IgM和IgG均保持稳定,移植肾功能良好。然而,从MMF换用米唑嘌呤(MZ)后,肾移植功能逐渐恶化,且这种恶化与抗血型抗体升高有关,主要是IgG升高。IgM抗体产生与IgG平行,但较弱。重新启用MMF后,随着肾功能恢复,抗血型抗体IgG的升高活性降至正常水平。
ABO血型不相容肾移植后使用MMF后抗血型抗体IgG下降,停用MMF后则升高。MMF似乎影响了肾移植后跨越血屏障产生抗血型抗体的B细胞群体。