Complement component 1q (C1q) and classical complement pathway (C1q/CP)

Complement component 1q (C1q) is the initiating protein of the classical complement pathway and a key member of the C1 complex, which also includes the serine proteases C1r and C1s. It functions as a pattern recognition molecule that binds to various ligands, such as the Fc regions of IgM and IgG in immune complexes, C-reactive protein, and apoptotic cell surfaces. This binding triggers a conformational change that activates C1r and C1s, initiating a proteolytic cascade that leads to the formation of C3 and C5 convertases, ultimately resulting in opsonization, inflammation, and cell lysis. Beyond its role in innate immunity, C1q is involved in non-canonical functions such as synaptic pruning in the developing and aging central nervous system. Dysregulation of the classical pathway is linked to several pathologies, including cold agglutinin disease (CAD), where it drives autoimmune hemolysis, and neurodegenerative disorders like Alzheimer's disease, where it contributes to pathological synapse loss. Therapeutic agents like sutimlimab and ANX005 target C1s and C1q, respectively, to selectively inhibit the classical pathway while sparing the alternative and lectin pathways. This selective approach aims to provide efficacy in complement-mediated diseases while potentially reducing the risk of broad immunosuppression associated with downstream complement blockade. Monitoring of therapy often involves biomarkers such as CH50 activity and levels of C4 or C1q. Safety concerns primarily involve an increased susceptibility to infections by encapsulated bacteria due to the role of the classical pathway in host defense.

Other names

C1 complexClassical complement pathwayC1q-C1r-C1s complexClassical pathway of complement

Inhibition of C1q ligand binding or C1s serine protease activity to prevent the formation of C3 and C5 convertases in the classical complement pathway.