免疫生物製劑治療自體免疫疾病之現在與未來：以紅斑性狼瘡為典範

The Emerging Roles of Biologic Target Therapy in Systemic Autoimmune Diseases: SLE as a Paradigm

紅斑性狼瘡為典型自體免疫失調系統疾病。紅斑性狼瘡免疫失調病理機轉牽涉到原始免疫與獲得性免疫途徑多重相互作用結果。自體抗原在免疫細胞死亡後過度形成，抗原清除無法完成，抗原呈現細胞被刺激分化及分泌重要細胞激素，以第一型干擾素為中心促進特殊免疫抗原細胞分化。細胞激素及細胞訊息不平衡導引T 細胞分化及活化，促進輔助型T 細胞（TH1，TH2，TH17）分化，抑制調節型T 細胞。B 細胞因免疫耐受性喪失而過度活化產生過量的自體抗體，形成免疫複合體，造成組織器官損傷。紅斑性狼瘡傳統免疫調節治療無特定目標，易形成過度免疫抑制的不良作用。本文回溯自體免疫系統疾病免疫失調機轉進一步探討紅斑性狼瘡免疫生物製劑治療之新進展。

Systemic lupus erythematosus (SLE) is the prototype systemic autoimmune disease. SLE is characterized by multiple immune regulation steps interplay between innate and adaptive immune systems. SLE pathogenesis involving complex trait disorder of cell death and immune clearance pathways leads to widespread loss of immune tolerance to self-antigen overload, cytokine and mediators of inflammation release and immune response cells differentiation. Type I Interferon alpha contributes to the progression of dendritic cell (antigen presenting cell) dysfunctions. The imbalance of cytokines and activation signal pathways that trigger T cell activation and differentiation results in over stimulated effect or T cells (TH1, TH2, TH17) differentiation and suppressed T regulatory cell differentiation. B cell hyperactivity by feedback loop network of adaptive immunity releasing pathogenic auto-antibodies and immune complexes formation ultimately plays a critical role in target organ damage. The conventional immune therapy of SLE often results in side effects of over suppressive immune targets. This article reviews the pathogenesis in systemic autoimmune diseases and the emerging role of new biologic target therapy in SLE.