Complement component C1q (C1q)

Complement component C1q is the recognition subcomponent of the C1 complex, serving as the primary initiator of the classical complement pathway. It is a large, multimeric protein composed of 18 polypeptide chains that form a structure resembling a bouquet of flowers, with six globular heads that bind to the Fc regions of IgM or IgG antibodies, C-reactive protein, or apoptotic cells [1, 2]. Upon binding, C1q undergoes a conformational change that activates the associated serine proteases C1r and C1s, triggering a proteolytic cascade that leads to opsonization, inflammation, and cell lysis [2]. Beyond its traditional immune functions, C1q plays a vital role in the central nervous system by tagging synapses for elimination by microglia, a process essential for brain development but one that can become pathological in neurodegenerative diseases like Alzheimer's and Huntington's [4]. In the context of autoimmunity, C1q deficiency is strongly linked to the development of systemic lupus erythematosus (SLE) due to impaired clearance of apoptotic debris [5]. Therapeutic strategies targeting C1q, such as the monoclonal antibodies ANX005 and ANX007, are currently being investigated to treat complement-mediated disorders by selectively blocking the classical pathway while leaving the alternative and lectin pathways intact [3].

Other names

C1q complexComplement C1qComplement component 1, q subcomponentC1Q

Drugs targeting C1q typically function as monoclonal antibodies that bind to the globular head or collagen-like tail of the C1q molecule. This binding sterically hinders the interaction between C1q and its activators, such as immune complexes or apoptotic cells, or prevents the recruitment and activation of the C1r and C1s proteases, thereby halting the classical complement cascade at its earliest stage [3, 4].