Complement C4-A

Complement C4-A is a precursor protein that generates non-enzymatic components of the classical, lectin, and GZMK complement pathways (UniProt: P0C0L4). Following cleavage by complement proteases, C4b acts as an opsonin, covalently attaching to pathogen surfaces and recruiting C2b to form C3 and C5 convertases, thereby initiating a cascade that marks pathogens for removal and strengthens adaptive immunity. The C4-A isotype preferentially forms amide bonds with immune aggregates and protein antigens.

UniProt documentation associates C4A mutations with complement component 4A deficiency, a rare complement pathway disorder linked to autoimmune diseases including systemic lupus erythematosus and glomerulonephritis. C4A deficiency impairs the classical complement pathway's regulatory mechanisms.

In Alzheimer's disease, C4-A is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 1.12 across four subcellular fractions in TMT-labeled proteomics analysis (Chaparral AD proteomics). This elevation suggests potential involvement of complement-mediated inflammatory pathways in AD pathogenesis.