Complement component 4A (C4A)

Complement component 4A is a large glycoprotein that plays an essential role in the classical and lectin pathways of the human complement system, which is a major part of innate immunity. It is encoded by the *C4A* gene within the HLA region on chromosome 6. Upon activation by serine proteases such as C1s or MASP2, it is cleaved into fragments including C4a and C4b. The major active fragment, *C4b*, covalently attaches to pathogen surfaces or altered self-tissues where it acts as an opsonin—marking targets for phagocytosis—and forms part of enzymatic complexes (convertases) that propagate downstream immune responses through cleavage/activation of other key proteins like *complement component 3* (*C3*) and *complement component 5* (*C5*)[2][3]. Deficiency or dysfunction in this protein leads to increased susceptibility to infections and autoimmune conditions such as systemic lupus erythematosus. The stable breakdown product *C4d* serves as a clinical biomarker for monitoring disease activity related to excessive classical/lectin pathway activation—including antibody-mediated transplant rejection. While no approved drugs currently target Complement component 4 directly, research into monoclonal antibodies or small molecules modulating its function is ongoing due to its central role at the interface between pathogen recognition, inflammation regulation, clearance mechanisms, and adaptive immune signaling.[1]

Other names

Complement C4-AC4Acomplement component 4complement component 4Ahuman leukocyte antigen class III histocompatibility antigencomplement system protein C4A

For drugs under investigation or theoretical approaches—mechanisms include inhibition of cleavage/activation or blocking interaction with other complement components.