The role of CD40-CD154 interactions in autoimmunity and the benefit of disrupting this pathway
The role of CD40-CD154 interactions in autoimmunity and the benefit of disrupting this pathway
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DOI：
10.1080/08916930400002386
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发表时间：
2004-09-01
期刊：
影响因子：
3.5
通讯作者：
Shoenfeld, Y
中科院分区：
文献类型：
--
作者：
Toubi, E;Shoenfeld, Y
发现许多组织损伤和免疫介导的病理（例如移植物释放）涉及CD40-CD40配体（CD40L，CD154）信号通路。在许多动物模型中，这种途径的破坏导致了这些模型中移植物存活的改善。 CD40-CD154相互作用还显示在自身免疫性的维持中起着重要作用，并且在全身性红斑狼疮（SLE）中产生自身抗体。已经在活性SLE，类风湿关节炎（RA）和其他自身免疫性疾病的患者的T细胞上检测到CD154的高级表达，表明此类细胞可以解释具有免疫附件分子在B细胞上的高级表达。活性疾病。在SLE，RA和Sjogren病中还报道了血清可溶性CD154的水平升高，与相关的自身抗体以及临床疾病活性相关。ANTI-CD154抗体疗法可预防自身抗体的生产和肾脏免疫复杂沉积。表明该途径的破坏可能是SLE的有益治疗方法。但是，应研究经过治疗的SLE患者的血栓栓塞事件的预期数量高于预期的病因，应考虑预防措施。
Many tissue injuries and immune mediated pathologies such as graft allo-rejections were found to involve CD40-CD40 ligand (CD40L, CD154) signaling pathway. The disruption of this pathway in many animal models led to the improvement of graft survival in these models. CD40-CD154 interactions were also shown to play a significant role in the maintenance of autoimmunity, and the production of auto-antibodies in systemic lupus erythematosus (SLE). High-level expression of CD154 has been detected on T cells from patients with active SLE, rheumatoid arthritis (RA) and other autoimmune diseases, indicating that such cells could account for the high-level expression of immune accessory molecules on B cells of patients with active disease. An increased serum level of soluble CD154 was also reported in SLE, RA, and Sjogren's disease in correlation with the relevant autoantibodies and with the clinical disease activity.Anti-CD154 antibody therapy prevents auto-antibody production and renal immune complex deposition in lupus nephritis, indicating that disruption of this pathway could be a beneficial treatment in SLE. However, the etiology of the higher than expected number of thromboembolic events in antiCD154 treated SLE patients should be investigated and preventive measures should be considered.