心脏移植术后抗体介导排斥反应研究现况与进展

Current status and progress on antibody-mediated rejection in heart transplantation

抗体介导排斥反应(AMR)是心脏移植术后重要的并发症,在国内目前尚未得到足够的重视和充分的研究。目前认为AMR是一个自病理到临床的系列演变过程,启动于免疫要素(抗体、补体)的积累、免疫活化最后终结于组织器官损伤。临床上涵盖了循环抗体沉默期、亚临床期及有症状的AMR期。AMR发病机制是免疫球蛋白与补体沉积在移植物微血管内引发的炎性反应,其中补体活化是关键环节;因此,心肌活检标本中免疫检测补体C4d及C3d阳性,结合组织病理学毛细血管损伤是确诊AMR的必要依据;无创性基因Allomap和供体来源细胞游离DNA检测是筛选和监测的有效手段,但不能作为AMR的确诊方法。AMR的治疗可依据临床分级联合采用:皮质类固醇、静脉注射免疫球蛋白、血浆置换或利妥昔单抗这些证实有效的抗免疫损伤措施;而抗CD52单抗、依库珠单抗、光化学疗法等技术的疗效尚待于进一步验证。

Antibody-mediated rejection(AMR)is proved to be a crucial complication in heart transplantation,which has not been well evaluated and studied in China.Nowadays,it is considered that AMR contains a series of evolution process from pathological changes to clinic manifestation,which starts with the accumulation of immune factors(such as antibody,complement),the activation of complement and ends with graft tissues injury.Clinically,AMR was classified as circulating antibody silent stage,sub-clinical stage and symptomatic AMR stage.The mechanism of AMR involved in an inflammatory reaction induced by deposition of immunoglobulins and complements within the microvessels of the grafts,in which the activation of complements played a core role.Therefore,immunological assay of C4d and C3d in endomyocardial biopsy specimens combined with evidence of histopathology capillaries injury were necessary for the diagnosis of AMR.While noninvasive gene detection with Allomap and donor-derived cell-free DNA were effective method serving as screening and monitoring AMR.Recommendations on management of AMR consisted a combination of corticosteroid,intravenous immune globulin,plasmapheresis or rituximab by scale of AMR,which were proven to be effective against immune injury.However,the efficacy of anti-CD52 monoclonal antibody,eculizumab and photochemotherapy remains to be further evaluated.