Complement C1q and downstream pathway proteins (C1q/Complement)

Complement C1q and its downstream proteins (C1r, C1s, C4, C2, C3, and C5-C9) constitute the classical pathway of the complement system, a critical arm of the innate immune response (Ricklin et al., 2010, Nature Immunology). C1q acts as a pattern recognition molecule that initiates the cascade upon binding to immune complexes, pathogens, or apoptotic cells, leading to the sequential activation of serine proteases (C1r, C1s) and the cleavage of central components C3 and C5 (Kolev et al., 2014, Nature Reviews Immunology). This process results in opsonization, recruitment of inflammatory cells via anaphylatoxins (C3a, C5a), and direct cell lysis through the membrane attack complex (MAC) (Noris & Remuzzi, 2013, Nature Reviews Nephrology). Beyond its role in immunity, C1q is essential for synaptic pruning in the developing and diseased brain, where it tags synapses for elimination by microglia (Stevens et al., 2007, Cell). Dysregulation of this pathway is implicated in various pathologies, including autoimmune disorders like systemic lupus erythematosus, hematologic conditions like paroxysmal nocturnal hemoglobinuria, and neurodegenerative diseases like Alzheimer's and Huntington's (Morgan, 2018, Nature Reviews Drug Discovery). Therapeutic strategies involve monoclonal antibodies or peptides that target specific nodes such as C1q (e.g., ANX005), C1s (e.g., sutimlimab), C3 (e.g., pegcetacoplan), or C5 (e.g., eculizumab) to mitigate tissue damage and chronic inflammation (Mastellos et al., 2019, Trends in Immunology).

Other names

Classical complement pathwayC1 complexComplement cascadeC1q-C9 pathway

Inhibition of the classical complement pathway initiation by blocking C1q or C1s, or preventing the formation of the membrane attack complex by inhibiting C3 or C5 cleavage.