The Role of the Complement System in Autoimmune Diseases and Therapeutic Targeting

The complement system, a critical component of the innate immune system, plays a dual role in immune defense and pathogenesis, particularly in autoimmune diseases. Comprising over 30 proteins, the complement system facilitates pathogen clearance, inflammation, and immune modulation. However, its dysregulation can lead to uncontrolled activation and contribute to the development and progression of various autoimmune disorders, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), antiphospholipid syndrome (APS), and vasculitis. In these diseases, excessive complement activation triggers inflammation, immune cell recruitment, and tissue damage, exacerbating the autoimmune response. This review provides an in-depth analysis of the complement system’s role in autoimmune diseases, exploring how its three activation pathways—classical, lectin, and alternative—contribute to disease pathogenesis. It also discusses key complement proteins such as C3, C5, and the membrane attack complex (MAC) in promoting inflammatory responses in these conditions. Moreover, the review highlights recent advances in therapeutic strategies targeting the complement system, including the development of C5 inhibitors like eculizumab and C3 inhibitors, which show promise in treating complement-mediated autoimmune diseases. These therapies aim to reduce inflammation and tissue destruction, offering new approaches for managing autoimmune disorders. Understanding complement dysregulation is crucial for the development of more effective treatments in the future. Keywords: Complement system, Autoimmune diseases, Complement activation, Inflammation, Therapeutic targeting