Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway
Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway
复制标题
DOI：
10.1182/blood2018-03-834598
复制
发表时间：
2018-12-06
期刊：
影响因子：
20.3
通讯作者：
Arepally, Gowthami M.
中科院分区：
文献类型：
--
作者：
Khandelwal, Sanjay;Ravi, Joann;Arepally, Gowthami M.
暴露于肝素引发许多（如果不是大多数）受体抗体应答的机制知之甚少。我们最近证明，抗原性血小板因子4（PF 4）/肝素复合物激活血浆中的补体并结合B细胞。在这里，我们描述了这个过程是如何启动的。当将PF 4/肝素加入健康供体的血浆中时，我们观察到补体激活的广泛稳定变化，表明应答者“表型”（高、中或低）。对这些健康献血者血浆的蛋白质组学分析显示，补体激活与血浆免疫球蛋白M（IgM）水平之间有很强的相关性（r = 0.898; P
The mechanisms by which exposure to heparin initiates antibody responses in many, if not most, recipients are poorly understood. We recently demonstrated that antigenic platelet factor 4 (PF4)/heparin complexes activate complement in plasma and bind to B cells. Here, we describe how this process is initiated. We observed wide stable variation in complement activation when PF4/heparin was added to plasma of healthy donors, indicating a responder "phenotype" (high, intermediate, or low). Proteomic analysis of plasma from these healthy donors showed a strong correlation between complement activation and plasma immunoglobulin M (IgM) levels (r = 0.898; P