Studies On The Pathogenesis Of Thrombotic Thrombocytopenic Purpura And The Expression Of ADAMTS13 In Tumor Cell Lines

Thrombotic thrombocytopenic purpura (TTP) is a lethally microvascular occlusive "thrombotic microangiopathy", and associated with von Willebrand factor-cleaving protease(ADAMTS13) severely deficientcy. The reasons which ADAMTS13 is absent in TTP are because: firstly, the mutation in ADAMTS13 leads to impairment in gene's synthesis and secretion; secondly, anti-ADAMTS 13 antibodies inhibit ADAMTS13's function and/or contribute to its cleareance. Unusually large von willebrand factor (ul-VWF) multimers are secreted by endothelial cells injuried by inciting factor, and these ul-VWF multimers bind more efficiently than normal VWF in plasma to platelet glycoprotein receptors under highly shear stress in microvascular. Ul-VWF multimers will be cleaved into small pieces by ADAMTS13, which prevents thrombi forming. Thus, the person with ADAMTS13 deficiency may present TTP. But it is proved that ADAMTS13 deficiency is not sufficient for TTP, there may be other triggers for this disease and we put some efforts on investigating them; since the structure of ADAMTS13 is associated with its function, we studied on how the mutants of ADAMTS13 worked; ADAMTS13 mRNA is detected in almost every organ tissue, recently, we detected it in some cell lines of cancer and investigate the difference in expression of ADAMTS13 when NB4 was treated by ATRA.Studies on the pathogenesis of TTP1, We evaluated AD AMTS13 antigen levels in TTP and other diseases.1) The average ADAMTS13 antigen level in Chinese normal(CN) plasma was 601 ± 145mU/ml (mean ± SD, n=26), compared to the level set at 1 U/ml in pooled (n=20) normal human plasma from Caucasian origin, which mean was 950±210 mU/ml,the mean levels in serum of normal control were 413±232 mU/ml (p<0.01) .2) In idiopathic TTP plasma, before plasma exchange (pre-PE), 99±82mU/ml (n=11) was detected (p<0.01 versus CN), which upon PE increased to 449.4±232.33mU/ml(p<0.01, n=10, versus pre-PE).The antigens of ADAMTS13 in secondary TTP...