Anti-C1QC polyclonal antibody

Complement is an enzyme cascade network composed of over 50 plasma and membrane proteins activated via the classical, lectin and other pathways. This classical pathway's first recognition molecule, C1q, identifies immune complexes, germs and damaged cells. C1q controls immune function, growth of tissue and pathology, especially immune tolerance, tumor immunity and autoimmune diseases. C1q is intricate in form and function. It consists of 18 polypeptide chains: six C1QA, six C1QB, and six C1QC chains. These chains compose a hexamer using specific pairing sequences, and each chain has a collagen-like domain (cC1q) on the N-terminus and a globular domain (gC1q) on the C-terminus. The globular C1q domain (gC1q) is able to recognize non-self ligands like pathogens, apoptotic cells and exosomes, as well as modified self-molecules like -amyloid and prion proteins. Its collagen-like structure allows C1q to associate with the C1r and C1s strands, activating the classic complement pathway. Its geometry allows C1q to discriminate ligands such as immune complexes (IgG and IgM), phosphatidylserine on death cells, -amyloid proteins, and pathogen surface molecules (e.g. viral proteins, bacterial membranes). Its versatility lets C1q operate between innate and adaptive immunity in a wide array of immunological and non-immune roles.

Figure 1. Schematic Representation of C1q Molecule Assembly (Source: Frachet, P., et al., 2015)

C1q activates the classical complement pathway. In this route, C1q interacts to immunological complexes (such IgG or IgM), activating C1r and C1s.This activation breaks the bonds of C4 and C2, generating the C3 convertase (C4b2b), which cuts C3 into C3b. C3b "opsonizes" the immune response, making the immune cells more effective at destroying pathogens, and it also creates the membrane assault complex (MAC), which damages the membrane of the pathogen cell.C1q's gC1q domain recognizes and binds to immune complexes or other ligands (pathogens, apoptotic cells, etc.), triggering the classic complement cascade. This pathway is central to antibody-mediated immune activation because it eliminates pathogens, inflamed cells, and even self-cells. For instance, C1q binding to phosphatidylserine on dying cells stimulates phagocytosis, decreasing the likelihood of an autoimmune response. Failure to completely flush apoptotic cells or defects in C1q signaling can lead to the production of autoantibodies, fueling the autoimmune pathology of systemic lupus erythematosus (SLE). Beyond its role in the classic complement system, there is now increasing evidence that C1q is complement-independent, specifically involved in tissue formation, inflammation and tumor immunity. For example, C1q is involved in placental development, angiogenesis and wound healing. C1q, according to studies, is highly expressed in the tumor microenvironment and participates in both the growth and proliferation of tumours.C1q also acts as an anti-cancer agent in some cancers by killing tumor cells or blocking the growth of tumours.C1q activates the tumor suppressor WOX1, for instance, which causes ovarian and prostate cancer cells to die. But in some cancers, like malignant pleural mesothelioma, C1q can also increase cell adhesion, migration and proliferation. As a result, the significance of C1q in tumor immunity must be separated based on tumor type, immune cell infiltration, and the local immunological microenvironment.

Figure 2. Immunohistochemical Analysis of C1q in Breast Cancer, Renal Cancer, and Lung Cancer (Source: Mangogna A, et al., 2019)

This relates to the function of C1q in the nervous system, which is also of interest. C1q in the CNS is shown to play a role not just in pruning synaptic neurons, but also in the course of neurodegenerative disease. As normal brain development continues, C1q drives synaptic deletion, an important feature of reworking neural networks.C1q binds to aberrant protein clumps like β-amyloid, potentially contributing to the advancement of neurodegenerative disorders like Alzheimer's. In some neurological disorders, C1q function may be unrelated to complement activation. C1q binding to β-amyloid may affect the activity of microglia and astrocytes, leading to neurodegenerative alterations, independent of the complement cascade. C1q expression is controlled by several transcription factors, including PU.1 and IRF8, which have been shown to activate C1q's promoter and regulate its synthesis in immune cells such as macrophages and dendritic cells. Studies further suggest that C1q expression is regulated by transcription factors specific to immune cells, such as MafB. Interestingly, the expression and function of C1q in tuberculosis (TB) have received significant attention. C1q levels are elevated in the serum of tuberculosis patients, which coincides with the typical signs of disease development. In particular, elevated C1q in TB patients is linked to an increased monocyte count, suggesting that C1q may be involved in TB immune surveillance. C1q increases activation of immune cells, especially monocytes and neutrophils. According to research, after TB infection, C1q synthesis interacts with Mycobacterium tuberculosis' immune evasion pathways, perhaps aiding in pathogen clearance. Finally, C1q deficiency has a substantial association with autoimmune illnesses such as systemic lupus erythematosus. Because of its involvement in removing apoptotic cells, C1q loss in patients causes a buildup of apoptotic cells, which trigger autoimmune reactions and autoantibodies, resulting in illness. According to studies, C1q deficiency is one of the most significant genetic risk factors for SLE, with around 85% of patients acquiring SLE-like symptoms. Clinically, immunological dysregulation caused by C1q deficiency causes organ damage, such as the skin and kidneys, and can lead to severe neuropsychiatric symptoms.

Anti-C1qC pAb
C1QC Complement Protein Antibody
Polyclonal Antibody to C1QC
Anti-C1qC Antibody