免疫功能异常在再生障碍性贫血发病中的作用及临床意义

目的 探讨可溶性CD40配体(SCD40L)、可溶性Fas配体(sFasL)及Flt3配体(FL)等多种免疫活性分子在再生障碍性贫血(AA)发病中的作用及临床意义。方法 采用常规Elisa方法测定34例AA患外周血和骨髓中sCD40L、sFasL和FL的含量；应用免疫荧光标记技术及流式细胞术分析法检测其T细胞亚群及活化相关膜表面分子；观察T细胞对骨髓粒一单核细胞集落(CFU-GM)试验的影响。结果 AA骨髓和外周血CD8^ 细胞百分数增加，CM4／CD8比例下降，骨髓中CD25^ 。和HLA-DR^ 细胞百分数增多；AA骨髓GM-CFU明显减少，急性AA尤为显，去除T淋巴细胞可使大部分患CFU-GM形成增加；绝大部分患sFasL含量增加，FL水平升高(达正常的20倍以上)，FL含量与临床疗效密切相关，治疗有效FL水平明显下降，但未达正常水平。sCD40L水平显降低，其含量直接反映患血小板数。结论 T细胞的异常活化及多种免疫活化分子异常增高是AA造血功能衰竭的主要原因之一。定期检测骨髓或外周血sCD40L、sFasL和FL有利于了解AA的病情变化及预后判断。

Effects of immunological factors on pathogenesis of aplastic anemia and its clinical significane

Objective To investigate the soluble CD40 ligand(sCD40L),soluble Fas ligand(sFasL) and flt-3 ligand(FL) in pathogenesis of aplastic anemia(AA) and its clinical significance.Method Elisa assay was employed to determine the levels of sCD40L,sFasL and FL in peripheral blood and bone marrow of 34 AA patients.Color immunofluorescence assay and flow cytometry analysis were used to trace the T cell subsets and membrane molecules.The effects of T cells on colony forming unit-granulocyte-macrophage(CFU-GM) was measured by colony forming assay in vitro with or without T lymphocyte depleted.Results Ratio of CD4/CD8 decreased and the proportion of CD8 cells in peripheral blood or bone marrow increased in AA patients.Expression of CD25 and HLA-DR increased in bone marrow of patients with AA.The numbers of GM-CFU decreased significantly in AA patients,especially in those with serious AA.But numbers of GM-CFU increased in most cases after T cells were depleted.The levels of sFasL and FL increased significantly in AA patients.The level of FL is as 20 times high as those in controls.Although the levels of FL decreased after effective treatment,this will not return to normal.The concentration of sCD40L decreased significantly in patients with AA.Statistic analysis showed that the levels of sCD40L were parallel to the numbers of patelet in peripheral blood of AA patients.Conclusion T cells abnormal activation and increasing levels of immunological molecules have great implication on pathogenesis on AA.Dynamic monitoring of the changes of sCD40L,sFasL and FL concentration in bone marrow or peripheral blood can provide useful information for diagnosis and prognosis in patients with AA.