Classical and lectin complement pathway components (CP/LP components)

The classical and lectin complement pathways are essential arms of the innate immune system that recognize and eliminate pathogens through a highly regulated proteolytic cascade. The classical pathway is primarily activated by the binding of the C1 complex (comprising C1q, C1r, and C1s) to antibody-antigen complexes, while the lectin pathway is triggered when mannose-binding lectin (MBL) or ficolins bind to specific carbohydrate patterns on microbial surfaces (StatPearls, 2023). Both pathways converge at the activation of specific serine proteases—C1s in the classical pathway and MASP-2 in the lectin pathway—which cleave complement components C4 and C2 to form the C3 convertase (UniProt, 2024). This activation leads to opsonization, the release of pro-inflammatory anaphylatoxins, and the assembly of the membrane attack complex (MAC) for direct pathogen lysis. Dysregulation of these pathways is a key driver in several autoimmune and inflammatory conditions, such as cold agglutinin disease, lupus nephritis, and IgA nephropathy (PubMed, 2022). Therapeutic interventions, including the C1s inhibitor sutimlimab and the MASP-2 inhibitor narsoplimab, are designed to selectively block these pathways to prevent tissue damage while preserving other immune functions (NIH, 2023). However, a significant safety concern with these therapies is the increased susceptibility to life-threatening infections from encapsulated bacteria, necessitating prophylactic vaccination (PubMed, 2021).

Other names

Classical complement pathwayLectin complement pathwayC1 complexMannose-binding lectin pathwayMBL pathwayComplement C1sMASP-2

Inhibition of the serine proteases C1s (classical pathway) or MASP-2 (lectin pathway) to prevent the cleavage of C4 and C2, thereby halting the formation of the C3 convertase and subsequent downstream inflammatory and cytolytic activities.