Zou Yizhou, Heinemann Falko M, Grosse-Wilde Hans, Sireci Guido, Wang Zhengnan, Lavingia Bhavna, Stastny Peter
Transplantation of Immunology Division, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8886, USA.
Hum Immunol. 2006 Mar;67(3):230-7. doi: 10.1016/j.humimm.2006.02.017. Epub 2006 Mar 30.
Previously we have reported on the development of antibodies against MICA alleles in kidney transplant recipients. These alloantibodies have now been determined using a new assay using Luminex beads bound to soluble recombinant MICA antigens produced in insect cells. In the present study we have analyzed sera from 85 kidney transplant recipients on the waiting list and 66 patients transplanted within the last 4 years and 59 acid eluates obtained from allograft nephrectomy specimens. Many of the patients in those groups were sensitized and some had previous transplants (waiting list: 15%; post-tx: 7.6%; eluates 22%) and their sera were found to contain anti-human leukocyte antigen (HLA) and anti-MICA antibodies. Anti-MICA antibodies were detected in 21/85 (24.7%) of the waiting list patients and in 15/66 (22.7%) of the transplanted recipients; 11 of the eluates (18.6%) were found to have MICA-specific antibodies (6 of them also had anti-HLA antibodies and 5 did not). These data suggested that immunization against mismatched MICA alleles induces development of anti-MICA antibodies. The finding of MICA allele-specific antibodies in eluates of kidney transplants suggests that anti-MICA antibodies can be involved in the pathogenesis of kidney allograft rejection. Further studies will be required to determine whether patients who produce alloantibodies against MICA alleles are at risk for transplant rejection even when no HLA antibodies are detected.
此前我们报道了肾移植受者中抗MICA等位基因抗体的产生情况。现在,这些同种异体抗体已通过一种新的检测方法得以确定,该方法使用与昆虫细胞中产生的可溶性重组MICA抗原结合的Luminex微球。在本研究中,我们分析了85名等待肾移植患者、66名在过去4年内接受移植的患者以及从移植肾切除标本中获得的59份酸洗脱液的血清。这些组中的许多患者已致敏,部分患者曾接受过移植(等待名单患者:15%;移植后患者:7.6%;洗脱液患者:22%),并且发现他们的血清中含有抗人类白细胞抗原(HLA)和抗MICA抗体。在等待名单患者的21/85(24.7%)和移植受者的15/66(22.7%)中检测到抗MICA抗体;11份洗脱液(18.6%)被发现含有MICA特异性抗体(其中6份还含有抗HLA抗体,5份不含)。这些数据表明,针对不匹配的MICA等位基因的免疫会诱导抗MICA抗体的产生。在肾移植洗脱液中发现MICA等位基因特异性抗体表明,抗MICA抗体可能参与肾移植排斥反应的发病机制。还需要进一步研究来确定产生抗MICA等位基因同种异体抗体的患者即使未检测到HLA抗体是否也有移植排斥的风险。