Complement C1s subcomponent

Complement C1s subcomponent (C1S) is a serine protease component of the complement C1 complex that initiates the classical complement cascade (UniProt: P09871). Upon activation by C1R following antigen-antibody complex formation, C1s cleaves and activates downstream complement components C2 and C4, which are essential for phagocytosis and pathogen elimination. C1s also cleaves C1 inhibitor and can modulate IGF1 signaling through IGFBP5 cleavage.

C1S is expressed as a circulating serum protein central to innate immune function. Genetic deficiency of C1S leads to C1 deficiency and increased susceptibility to immune complex diseases resembling systemic lupus erythematosus (UniProt: P09871). Mutations in C1S have also been associated with Ehlers-Danlos syndrome, periodontal type 2, a connective tissue disorder with early-onset periodontal disease.

In Alzheimer's disease, C1S is upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: 0.7155; Chaparral AD proteomics). This elevation suggests activation of classical complement cascade signaling in the AD brain, which may contribute to neuroinflammation and neurodegeneration observed in the disease.