Koutouzov Sophie, Mathian Alexis, Dalloul Ali
INSERM U 764 and Université Paris XI, 32 Rue des Carnets, Clamart, France.
Autoimmun Rev. 2006 Oct;5(8):554-62. doi: 10.1016/j.autrev.2006.05.002. Epub 2006 Jun 27.
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by the production of autoantibodies directed against nuclear antigens and chronic inflammation affecting multiple tissues. Complex genetic disorders are at the origin of the disease in humans and in SLE-prone mice, leading to the escape of auto-reactive B-lymphocytes from central and peripheral control checkpoints that operate normally in healthy organisms. Although necessary, autoimmune B-cells are not sufficient and additional mechanisms such as T-cell help are clearly needed for the disease to occur. The role of type-I interferons (type-I IFNs), and in particular IFNalpha, as prominent cofactors for SLE was suggested years ago. Leading observations in patients and recent data in SLE-prone mice have now established IFNalpha as a major actor in SLE. Several systemic clinical symptoms and laboratory findings can indeed be interpreted as downstream effects of a high IFNalpha production, and point to this cytokine as a link between the expansion of autoimmune B-cells and the stimulation of other components of the immune system. Consequently, a vicious circle is established with overt immune-cell activation and inflammatory infiltrates culminating in the selective destruction of tissue targets, notably the kidney. These notions can now be transplanted to the clinic and designate IFNalpha as a new promising therapeutic target.
系统性红斑狼疮（SLE）是一种典型的自身免疫性疾病，其特征是产生针对核抗原的自身抗体以及影响多个组织的慢性炎症。复杂的遗传疾病是人类和易患SLE小鼠发病的根源，导致自身反应性B淋巴细胞逃避在健康生物体中正常运作的中枢和外周控制关卡。虽然自身免疫性B细胞是必要的，但并不充分，显然疾病的发生还需要其他机制，如T细胞辅助。多年前就有人提出I型干扰素（I型IFN），特别是IFNα，作为SLE的重要辅助因子的作用。患者的主要观察结果和易患SLE小鼠的最新数据现已确定IFNα是SLE的主要参与者。实际上，几种全身临床症状和实验室检查结果可以解释为高IFNα产生的下游效应，并表明这种细胞因子是自身免疫性B细胞扩增与免疫系统其他成分刺激之间的联系。因此，形成了一个恶性循环，明显的免疫细胞激活和炎症浸润最终导致组织靶标，特别是肾脏的选择性破坏。现在这些概念可以应用于临床，并将IFNα指定为一个新的有前景的治疗靶点。
