Complement component 1q

Complement component 1q (C1q) is a protein complex that plays a crucial role in the immune system, particularly in the classical pathway of the complement system. This system is a major part of the innate immune response, providing a rapid defense against pathogens. C1q is the first component of the complement system to act in the classical pathway, where it binds to antibodies that are attached to pathogens, initiating a series of reactions that lead to the destruction of the pathogen.

Structure and Function

C1q is a complex molecule made up of 18 polypeptide chains: six A-chains, six B-chains, and six C-chains. These chains are arranged in a bouquet-like structure, with a collagen-like region and a globular domain. The globular domain is responsible for recognizing and binding to the Fc region of antibodies (IgG and IgM) that are bound to antigens on the surface of pathogens.

Upon binding to antibodies, C1q undergoes a conformational change that activates the C1r and C1s serine proteases, which are associated with C1q in the C1 complex. This activation leads to the sequential activation of other complement components, resulting in opsonization of pathogens, recruitment of inflammatory cells, and lysis of the pathogen's cell membrane through the formation of the membrane attack complex (MAC).

Role in Disease

While C1q is essential for the clearance of pathogens, dysregulation of the complement system can lead to various diseases. Deficiencies in C1q are associated with an increased susceptibility to infections and a higher risk of developing autoimmune diseases, such as systemic lupus erythematosus (SLE). In SLE, the absence or reduced levels of C1q can lead to impaired clearance of apoptotic cells and immune complexes, contributing to the autoimmune response.

Moreover, excessive activation of C1q and the complement system can contribute to tissue damage in autoimmune and inflammatory diseases. In conditions such as rheumatoid arthritis, ischemia-reperfusion injury, and Alzheimer's disease, inappropriate activation of the complement system, including C1q, can exacerbate tissue inflammation and damage.

Clinical Significance

The measurement of C1q levels and function can be used in the diagnosis and monitoring of diseases associated with complement system dysregulation. Therapeutic interventions targeting C1q and the complement system are being explored as potential treatments for autoimmune diseases, inflammatory conditions, and certain types of cancer, where complement activation plays a role in disease pathology.

Research Directions

Research on C1q is focused on understanding its role in the immune system and disease, developing therapies that can modulate its activity, and exploring its potential as a biomarker for disease. Studies are also investigating the role of C1q in neurodegenerative diseases, where it is involved in the clearance of amyloid-beta plaques, a hallmark of Alzheimer's disease.