Thrombogenicity of TNFα in rheumatoid arthritis defined through biological probes:: TNFα blockers
Thrombogenicity of TNFα in rheumatoid arthritis defined through biological probes:: TNFα blockers
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DOI：
10.1016/j.autrev.2003.09.004
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发表时间：
2004-06-01
影响因子：
13.6
通讯作者：
Gremese, E
中科院分区：
文献类型：
--
作者：
Ferraccioli, G;Gremese, E
类风湿性关节炎是一种心血管风险很高的疾病。最近的研究表明，病程超过10年的RA患者患心肌梗死的风险是骨关节炎对照组的三倍以上。主要的决定因素被认为是慢性炎症过程，由一些关键的细胞因子驱动，其中肿瘤坏死因子α被认为在大多数患者中起主导作用。因此，一旦被特定的抑制剂如肿瘤坏死因子α阻滞剂(Infliximab，Etanercept)阻断，应该会大大降低心血管风险。然而，尽管在一小部分患者中，肿瘤坏死因子受体阻滞剂可诱导自身免疫的出现。这种自身免疫被认为是由于一旦全身炎症(CRP，SAP)被特定的阻滞剂控制后，凋亡小体被清除得很差，以及缺乏对某些产生特定自身抗原抗体的B细胞群的控制。在肿瘤坏死因子阻断过程中产生的自身抗体中，抗心磷脂似乎是对心血管风险最关键的。抗心磷脂在临床上的显著水平似乎由两种可能的机制驱动，一种是由于在阻断可溶性肿瘤坏死因子α时常见的尿路或上呼吸道感染，另一种是由于在阻断可溶性膜性肿瘤坏死因子α时一些自身反应性B细胞逃逸所致。由于与感染相关的自身抗体以及与感染无关的高水平抗体都可以通过适当的治疗得到很好的控制，临床医生在它成为临床问题之前应该注意这种生物学现象。(C)2003爱思唯尔B.V.保留所有权利。
Rheumatoid arthritis is a disease at high cardiovascular risk. It has recently been shown that RA patients with more than 10 years disease duration present a risk of myocardial infarction more than three times higher than osteoarthritis controls. The major determinant is thought to be the chronic inflammatory process, driven by some key cytokines among which TNFalpha is thought to play the leading role in the majority of the patients. TNFalpha, therefore, once blocked by specific inhibitors like TNFalpha blockers (Infliximab, Etanercept) should profoundly decrease the cardiovascular risk. However, TNF blockers induce the appearance of autoimmunity though in a small minority of the patients. This autoimmunity is thought to be due to the poor clearance of apoptotic bodies once the systemic inflammation (CRP, SAP) is controlled by the specific blockers, and to the lack of control of some B cell populations producing autoantibodies to specific autoantigens. Among the autoantibodies arising during TNF blockade, anticardiolipin appear to be the most crucial with respect to the cardiovascular risk. The appearance of anticardiolipins at clinically significant levels appears to be driven by two possible mechanisms, one due to common infections of the urinary or upper airways tract during blockade of soluble TNFalpha, the other due to the escape of some autoreactive B cells during blockade of soluble and membranous TNFalpha. Since both autoantibodies related to infections as well as the high levels unrelated to infections, can be well controlled by appropriate therapies, clinicians should pay attention to the biological phenomenon before it becomes a clinical problem. (C) 2003 Elsevier B.V. All rights reserved.