Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brazil.
Clinics (Sao Paulo). 2010 Mar;65(3):327-33. doi: 10.1590/S1807-59322010000300014.
Systemic lupus erythematosus is a prototypical autoimmune disease characterized by the deregulation of T and B cells, tissue infiltration by mononuclear cells, tissue damage and the production of autoantibodies. There is a consensus that accelerated apoptosis of circulating lymphocytes and/or impaired clearance of apoptotic bodies may increase the amount of nuclear antigens presented to T lymphocytes. This process is accompanied by autoimmune responses that can lead to the development of lupus. The dysfunction of apoptosis may be a direct consequence of alterations in proteins/genes such as Fas, Bcl-2 and C1q. Increased expression of Fas antigen could intensify the exposure of hidden antigens. The overexpression of Bcl-2 protein might inhibit the removal of auto-reactive cells, and the lack of C1q could impair the clearance of self-antigens. The complete knowledge of the role of apoptosis components in the etiopathogenesis of lupus could lead to the development of new therapies targeting the apoptotic threshold, which could result in a more specific and effective disease response compared to global immunosuppression. This review summarizes the role of each component of the apoptotic process in the pathogenesis of lupus.
系统性红斑狼疮是一种典型的自身免疫性疾病，其特征是 T 细胞和 B 细胞失调、单核细胞浸润组织、组织损伤和产生自身抗体。人们普遍认为，循环淋巴细胞的加速凋亡和/或凋亡小体的清除受损可能会增加呈递给 T 淋巴细胞的核抗原数量。这一过程伴随着自身免疫反应，可能导致狼疮的发生。凋亡功能障碍可能是 Fas、Bcl-2 和 C1q 等蛋白/基因改变的直接后果。Fas 抗原的过度表达可能会加剧隐匿抗原的暴露。Bcl-2 蛋白的过度表达可能会抑制自身反应性细胞的清除，而 C1q 的缺乏则会损害自身抗原的清除。对凋亡成分在狼疮发病机制中的作用的全面了解可能会导致针对凋亡阈值的新疗法的发展，与全身免疫抑制相比，这种新疗法可能会导致更具针对性和更有效的疾病反应。本综述总结了凋亡过程中每个成分在狼疮发病机制中的作用。
