Antiphospholipid syndrome: Complement activation, complement gene mutations, and therapeutic implications.
Antiphospholipid syndrome: Complement activation, complement gene mutations, and therapeutic implications.
复制标题
抗磷脂综合征：补体激活、补体基因突变和治疗意义。
DOI：
10.1111/jth.15082
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Brodsky RA
中科院分区：
文献类型：
--
作者：
Chaturvedi S;Braunstein EM;Brodsky RA
抗磷脂综合征（APS）是一种获得性血栓炎性疾病，其特征是存在抗磷脂抗体以及静脉或动脉血栓形成和/或产科发病率增加。疾病谱从无症状到以广泛血栓形成和多器官衰竭为特征的严重形式，称为灾难性APS（CAPS）。CAPS仅影响约1%的APS患者，通常表现为血栓性微血管病，尽管有最好的治疗方法，但仍有>40%的死亡率。动物模型表明，补体与APS血栓形成的病理生理学有关，最近的人体研究数据证实了凝血和补体途径之间的相互作用。通过抗磷脂抗体激活补体级联可引起细胞损伤并通过多种机制促进凝血。最后，类似于经典的补体介导的疾病，如非典型溶血性尿毒综合征，一个子集的APS患者可能会增加发展CAPS的风险，因为在补体调节的关键基因的种系变异的存在。总之，这些数据使补体抑制成为一种有吸引力的和潜在的挽救生命的疗法，以减轻严重血栓性APS和CAPS的发病率和死亡率。
Antiphospholipid syndrome (APS) is an acquired thromboinflammatory disorder characterized by the presence of antiphospholipid antibodies as well as an increased frequency of venous or arterial thrombosis and/or obstetrical morbidity. The spectrum of disease varies from asymptomatic to a severe form characterized by widespread thrombosis and multiorgan failure, termed catastrophic APS (CAPS). CAPS affects only about ~1% of APS patients, often presents as a thrombotic microangiopathy and has a fulminant course with >40% mortality, despite the best available therapy. Animal models have implicated complement in the pathophysiology of thrombosis in APS, with more recent data from human studies confirming the interaction between the coagulation and complement pathways. Activation of the complement cascade via antiphospholipid antibodies can cause cellular injury and promote coagulation via multiple mechanisms. Finally, analogous to classic complement-mediated diseases such as atypical hemolytic uremic syndrome, a subset of patients with APS may be at increased risk for development of CAPS because of the presence of germline variants in genes crucial for complement regulation. Together, these data make complement inhibition an attractive and potentially lifesaving therapy to mitigate morbidity and mortality in severe thrombotic APS and CAPS.
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影响因子：
20.3
作者：
Chaturvedi, Shruti;Braunstein, Evan M.;Brodsky, Robert A.
通讯作者：
Brodsky, Robert A.
影响因子：
5.7
作者：
Chaturvedi, Shruti;Alluri, Ravi;McCrae, Keith R.
通讯作者：
McCrae, Keith R.
影响因子：
8.3
作者：
Burwick, Richard M.;Fichorova, Raina N.;Feinberg, Bruce B.
通讯作者：
Feinberg, Bruce B.
影响因子：
2.6
作者：
de Larrañaga, GF;Remondino, GI;San Jaun, JA
通讯作者：
San Jaun, JA
影响因子：
20.3
作者：
Agostinis, Chiara;Durigutto, Paolo;Tedesco, Francesco
通讯作者：
Tedesco, Francesco