Lectin complement pathway (LCP)

The lectin complement pathway is a critical component of the innate immune system that triggers a cascade of proteolytic events to eliminate pathogens and damaged cells (StatPearls, 'Complement System'). It is initiated by the binding of pattern recognition molecules, such as mannose-binding lectin (MBL) or ficolins, to specific carbohydrate patterns on the surface of microorganisms. This binding activates MBL-associated serine proteases (MASPs), particularly MASP-2, which then cleaves complement components C4 and C2 to form the C3 convertase. While essential for host defense, dysregulation or overactivation of the lectin pathway is implicated in various inflammatory and autoimmune diseases, including hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) and IgA nephropathy (PMID: 31511841). Therapeutic strategies often focus on inhibiting MASP-2 to selectively block this pathway while leaving the classical and alternative pathways intact, potentially offering a better safety profile than broad complement inhibition (PMID: 33456231). Drugs like narsoplimab are designed to bind MASP-2 and prevent the formation of the C3 and C5 convertases, thereby reducing tissue damage and systemic inflammation. This targeted approach is currently being evaluated for its efficacy in treating rare complement-mediated disorders where the lectin pathway plays a dominant role.

Other names

Mannose-binding lectin pathwayMBL pathwayMASP-2-dependent pathwayMannan-binding lectin pathway

Inhibition of MASP-2 (Mannan-binding lectin-associated serine protease-2) prevents the cleavage of complement components C4 and C2, thereby blocking the formation of the C3 convertase (C4b2a) and subsequent downstream complement activation (PMID: 33456231).