Ficolins

Ficolins are soluble pattern recognition receptors that form part of the innate immune system and contribute to the lectin pathway of complement activation. In humans, three ficolins have been described: ficolin-1 (M-ficolin), ficolin-2 (L-ficolin), and ficolin-3 (H-ficolin), encoded by FCN1, FCN2, and FCN3. They share a common architecture consisting of an N-terminal collagen-like domain and a C-terminal fibrinogen-like recognition domain and organize into oligomeric structures that increase binding avidity to target surfaces.

Ficolin-1 is mainly expressed by neutrophils and, to a lesser extent, monocytes; ficolin-2 and ficolin-3 are primarily produced by the liver and circulate in the bloodstream. The ligands recognized by ficolins include acetylated compounds such as N-acetylglucosamine and other acetylated macromolecules found on a range of microbes, as well as certain altered-self ligands on apoptotic cells.

Upon binding to its targets, a ficolin associates with MASP family serine proteases, most notably MASP-2, to activate the lectin pathway. This leads to cleavage of C4 and C2, formation of the C3 convertase, opsonization, inflammation, and, ultimately, pathogen elimination.

Clinical relevance for ficolins includes genetic and serum level variations that influence susceptibility to infections, particularly in infancy or immunocompromised individuals. Deficiencies or functional alterations in FCN genes can be associated with increased infection risk and dysregulated inflammatory responses. Ficolin levels and genetics are not routine diagnostic tests but are studied as potential biomarkers in certain infectious and inflammatory contexts.