Complement components and autoantibodies

The term Complement components and autoantibodies refers to the pathological interaction between the innate complement system and the adaptive immune system's self-reactive antibodies [1]. In many autoimmune diseases, autoantibodies bind to self-antigens, triggering the classical complement pathway via the C1 complex, which initiates a cascade of proteolytic activations [1, 2]. This process leads to the generation of anaphylatoxins (C3a, C5a) that recruit inflammatory cells and the formation of the membrane attack complex (MAC), which causes direct cell lysis and tissue damage [3, 5]. Therapeutic strategies in this area focus on inhibiting specific complement proteins, such as C1s, C3, or C5, to halt the destructive cascade initiated by these autoantibodies [4, 6]. This approach is clinically validated in conditions like Myasthenia Gravis, Neuromyelitis Optica Spectrum Disorder, and Paroxysmal Nocturnal Hemoglobinuria, where complement-mediated damage is a primary driver of pathology [3, 4]. By targeting these components, clinicians can mitigate severe inflammation and tissue destruction even while the underlying autoantibody production persists [5, 6].

Other names

Complement systemAutoantibody-mediated complement activationHumoral immune effectorsClassical complement pathway

Inhibition of specific complement cascade proteins (e.g., C1s, C3, C5) or their receptors (C5aR1) to block the inflammatory and cytolytic pathways activated by autoantibodies.