MNS血型系统抗Mur导致胎儿低增生性贫血的机制研究

MNS血型系统杂交糖蛋白GP.Mur在我国南方人群中的分布频率高达10%。在免疫暴露时，GP.Mur能刺激机体产生同种抗体，引起严重输血反应及胎儿水肿，甚至死胎等，在输血医学及围产医学中意义重大。以往研究表明抗Mur主要通过免疫性溶血引起胎儿贫血，但我们发现抗Mur引起水肿的胎儿脐血网织红细胞计数降低。此外，我们利用已建立的前体红细胞培养方法，初步发现抗Mur能在体外抑制GP.Mur阳性前体红细胞的增殖。据此我们推测抑制前体红细胞增殖可能是抗Mur导致胎儿贫血的另一重要机制。本研究拟进一步证实抗Mur抑制前体红细胞增殖这一作用，并从抗Mur是否下调前体红细胞表面EPO受体、是否抑制其细胞周期、是否诱导其细胞凋亡及是否引发其被单核细胞吞噬清除4个方面探讨抗Mur抑制前体红细胞增殖的作用机理，阐明抗Mur导致胎儿低增生性贫血的机制，从而为临床预防及治疗抗Mur引起的胎儿贫血、水肿提供新思路。

MNS hybrid glycophorin GP.Mur distributed with a frequency of 10% in Southern China, which is clinically significant in transfusion medicine and perinatal medicine, because it can stimulate individuals to produce alloantibodies during immune exposure, causing severe transfusion reaction, neonatal and fetal anemia, hydrops foetalis and even fetal death. According to the previous studies, anti-Mur causes fetal anemia mainly through immune hemolysis, but we found a decreased reticulocytes count in the fetus with hydrops due to anti-Mur. Also, our preliminary data revealed that anti-Mur can inhibit the proliferation of cultured erythroid progenitor cells isolated from GP.Mur positive cord blood. These findings suggest that inhibition of the proliferation of erythroid progenitor cells is probably another important mechanism of fetal anemia duo to anti-Mur. In this study, we plan to confirm the function and elucidate the mechanism of anti-Mur inhibiting the proliferation of erythroid progenitor cells, as well as explore the mechanism of anti-Mur causing fetal hyporegenerative anemia, through analyzing whether anti-Mur reduces the expression of EPO receptor on the erythroid progenitor cells, inhibits the cell cycles, induces apoptosis, and activates immune phagocytosis of the cultured erythroblasts. This study will provide new thought for clinical prevention and treatment of fetal anemia due to anti-Mur.