Complement component 1q (C1q) and the classical complement pathway (C1q)

Complement component 1q (C1q) is the recognition protein that initiates the classical complement pathway, a vital component of the innate immune system (UniProt P02745). It exists as a large multimeric complex that binds to the Fc regions of IgM or IgG antibodies, or directly to pathogen surfaces and apoptotic cells (PubMed: 28814932). This binding triggers the activation of C1r and C1s proteases, leading to a cascade that cleaves C4, C2, and C3, ultimately resulting in the formation of the membrane attack complex (MAC) and the release of inflammatory mediators like C5a (StatPearls: Complement System). Beyond its immune role, C1q is essential for synaptic pruning in the developing central nervous system and the maintenance of tissue homeostasis by clearing cellular debris (PubMed: 23157122). Pathological activation of C1q and the downstream cascade is linked to neurodegenerative conditions like Alzheimer's disease and autoimmune disorders such as systemic lupus erythematosus (PubMed: 30224612). Therapeutic targeting of this pathway includes agents like ANX005, which blocks C1q directly, and downstream inhibitors like eculizumab (C5) or pegcetacoplan (C3) to treat complement-mediated hemolytic and neurological diseases (ClinicalTrials.gov: NCT04535401).

Other names

C1 complexComplement C1qClassical complement pathwayC1q subcomponentComplement C1

Inhibition of C1q binding to prevent classical pathway initiation, or blockade of downstream components such as C3 and C5 to prevent opsonization, anaphylatoxin release, and membrane attack complex (MAC) formation (PubMed: 31515306).