Complement factor H

Complement Factor H (CFH) is a 1231-amino acid glycoprotein that functions as a soluble inhibitor of the complement alternative pathway (UniProt: P08603). It maintains immune homeostasis by binding self-markers to prevent complement activation on cell surfaces, accelerates decay of the C3 convertase C3bBb, and acts as a cofactor for factor I-mediated C3b degradation. CFH also mediates cellular responses through interactions with receptors such as CR3/ITGAM on neutrophils.

CFH is implicated in multiple diseases affecting the eye and kidney. UniProt associations include age-related macular degeneration (ARMD4), basal laminar drusen, complement factor H deficiency, and atypical hemolytic uremic syndrome, indicating its critical role in complement regulation across tissues.

In Alzheimer's disease, CFH is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.43 (Chaparral AD proteomics). This elevation may reflect dysregulation of the alternative complement pathway, a process implicated in neuroinflammation and neurodegeneration associated with AD pathology.