去糖基化CD36单抗用于预防CD36抗体引起的FNAIT免疫治疗研究

研究证实，I型CD36缺失者经输血或怀孕过程有诱导CD36抗体产生的危险。而中国人群CD36I型缺失率约0.5%，是引起FNAIT发生的重要因素，但尚未见CD36抗体介导FNAIT发生的免疫治疗研究。本项目拟在前期研究基础上，开展去糖基化修饰CD36单抗预防CD36抗体引起的FNAIT治疗研究。通过血小板免疫和单抗制备获得IgG型抗鼠CD36单抗，以糖苷酶水解抗鼠CD36-IgG的Fc段聚糖，经抗体胎盘转运及结合特性分析，血小板吞噬和血小板清除实验这三方面研究，明确去糖基化抗鼠CD36-IgG与CD36的结合特性及其胎盘转运功能，阐明去糖基化抗鼠CD36-IgG竞争抑制CD36抗体对CD36+/+或CD36-/+血小板的吞噬清除作用，利用CD36抗体介导的FNAIT小鼠模型，证实去糖基化抗鼠CD36-IgG对FNAIT的免疫治疗效果，为今后其临床产前免疫治疗提供重要理论和技术支持。

The study confirmed that individuals with CD36 type I deficiency may be at risk of developing anti-CD36 antibodies after receiving transfusion or during pregnancy. However, the CD36 type I deficiency in Chinese populations was about 0.5%, which is the important factor for inducing FNAIT. But the immunotherapy of FANIT caused by CD36 antibody is still unknown. This project will research for the immunotherapy of FNAIT induced by CD36 antibody, which could be prevented by deglycosylated CD36 monoclonal antibody. The murine anti-mouse CD36 mAb, IgG subtype, was obtained by platelets immunization and the preparation of monoclonal antibody. Then the glucosidase was used to hydrolyze the Fc fragment of anti-mouse CD36-IgG. Through three studies on assessment of transplacental maternofetal transport and antibody-binding characterization using SPR, platelet phagocytosis and clearance assay, to clear the antibody-binding characterization of deglycosylated anti-mouse CD36-IgG with CD36 and its placental transfer function, and to elucidate its inhibition on CD36+/+ or CD36-/+ platelet phagocytosis and clearance caused by CD36 antibody. On the basis of FNAIT mouse model induced by CD36 antibody, to demonstrate that deglycosylated anti-mouse CD36-IgG could be used to prevent the FNAIT. In totally, the performance of this project will help to supply important theoretical and technical support for clinical antenatal immunotherapy of FNAIT caused CD36 antibody.