Allo-HSCT后NEU1介导GPIbα去唾液酸化在持续性血小板减少症发生机制中的作用

项目名称： Allo-HSCT后NEU1介导GPIbα去唾液酸化在持续性血小板减少症发生机制中的作用

项目编号： No.81470343

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张晓辉

作者单位： 北京大学

项目金额： 70万元

中文摘要： 持续血小板减少症（PT）是异基因造血干细胞移植（allo-HSCT）后严重的合并症，PT患者长期生存显著减低，进一步阐明PT发病机制，有重要的临床和理论意义；在前期研究中，首次发现PT患者的NEU1介导GPIbα去唾液酸化是移植后PT的特征性改变；并与产生GPIbα抗体B细胞密切关联，这一发现目前国内外未见报道。强烈提示NEU1对血小板GPIbα去唾液酸化，CD22+B细胞异常活化，可能在PT发病中起关键作用；本课题拟进一步深入研究NEU1/GPIbα对去唾液酸化的作用；初步阐明NEU1/GPIbα对PT患者血小板和巨核细胞的作用，探讨其对β-半乳糖和ST6GaI的影响；NEU1/GPIbα可能成为预测移植后PT特异的生物标记物，去唾液酸化的GPIbα有望成为临床潜在治疗靶点，为临床移植后PT的防治策略提供新的理论依据。

中文关键词： 异基因造血干细胞移植；移植免疫；T细胞；异基因骨髓移植；调节性树突状细胞

英文摘要： Prolonged thrombocytopenia (PT) is a severe complication after allo-hematopoietic stem cell transplantation (allo-HSCT). Long-time survival of PT patients is much shorter compared with others. Therefore, further investigation into the mechanism of prolonged thrombocytopenia is of great significance both clinically and theoretically. Our previous study first demonstrated that NEU1 mediated GPIbα desialylation is a character of patients with prolonged thrombocytopenia after HSCT and is closely related to B lymphocytes producing antibodies against GPIbα. This discovery strongly suggest that NEU1 mediated GPIbα desialylation and B cell abnormally activation may play a key role in the development of PT and this theory has never been published before. This project is designed to further investigate the function of NEU1/GPIbα to GPIbα, aiming to interpret its role on platelets and megakarycytes of PT patients as well as its impact on β-galactose and ST6Gal. NEU1/GPIbα may become a specific biological marker to predict the occurrence of prolonged thrombocytopenia after allo-HSCT. Desialylated GPIbα is a potential target for therapy and may provide a theoretical foundation of prevention and treatment of prolonged thrombocytopenia after HSCT.

英文关键词： allo-HSCT;transplantation immune;T cell;allo-BMT;regular dentritic T cell