Blood group antigen A on von Willebrand factor is more protective against ADAMTS13 cleavage than antigens B and H
Blood group antigen A on von Willebrand factor is more protective against ADAMTS13 cleavage than antigens B and H
复制标题
DOI：
10.1111/jth.14444
复制
发表时间：
2019-06-01
影响因子：
10.4
通讯作者：
Matsumoto, Masanori
中科院分区：
文献类型：
--
作者：
Hayakawa, Masaki;Kato, Seiji;Matsumoto, Masanori
ADAMTS 13特异性切割VWF-A2结构域中Y1605和M1606之间的肽键。目的VWF中含有ABO（H）血型抗原，可能影响VWF对ADAMTS 13的易感性。方法利用特异性识别Y1605残基的单克隆抗体，建立了双抗体夹心ELISA法，定量分析ADAMTS 13对VWF-DP的产生。结果使用VWF多聚体分析，与高分子量多聚体的减少相比，暴露于四种不同程度的高剪切应力后VWF-DP的产生得到验证。在259名健康个体的血浆分析中，O型血中VWF抗原（VWF：Ag）的血浆水平显著低于其他组，并且与血浆VWF-DP水平显著相关。O型血VWF-DP与VWF：Ag比值明显高于A、AB型血。B型血的比值也显著高于A型和AB型血，但与O型血无差异。最后，为了检测ABO（H）血型抗原是否有助于VWF裂解，使用锥板剪切应力诱导器将82份血浆样品暴露于高剪切应力。高切应力前后O型血VWF-DP/VWF：Ag比值的差异显著大于A、AB型血。结论VWF上A血型抗原比B和H血型抗原对ADAMTS 13的切割具有更强的保护作用。
Background ADAMTS13 specifically cleaves the peptide bond between Y1605 and M1606 within the VWF-A2 domain. Objective The VWF contains ABO(H) blood group antigens, which may influence the susceptibility of VWF to ADAMTS13. Methods Using a unique monoclonal antibody recognizing the Y1605 residue, we have developed a sandwich ELISA to analyze the generation of a VWF-DP by ADAMTS13 quantitatively. Results Production of VWF-DP after exposure to four different degrees of high shear stress was validated in comparison to the reduction in high-molecular-weight multimers using VWF multimer analysis. In analysis of plasma from 259 healthy individuals, plasma levels of VWF antigen (VWF:Ag) were significantly lower in blood group O than in the other groups and were significantly correlated with plasma VWF-DP levels. The ratio between VWF-DP and VWF:Ag was significantly higher in blood group O than in blood groups A and AB. The ratio in blood group B was also significantly higher than those in A and AB, but did not differ from blood group O. Finally, to examine whether ABO(H) blood group antigens contributed to VWF cleavage, 82 plasma samples were exposed to high shear stress using a cone-plate shear stress inducer. The difference in the VWF-DP/VWF:Ag ratio before and after high shear stress in blood group O was significantly greater than those in groups A and AB. Conclusion These results indicate that blood group antigen A on VWF was more protective against ADAMTS13 cleavage than antigens B and H.