Complement factor D

Complement factor D (CFD) is a protein that plays a crucial role in the immune system, specifically within the alternative pathway of the complement system. The complement system is a part of the innate immune system, responsible for enhancing the ability of antibodies and phagocytic cells to clear pathogens from an organism. Complement factor D is a serine protease that acts by cleaving Factor B when it is complexed with C3b, producing the active C3 convertase of the alternative pathway, C3bBb. This process is essential for the amplification loop of the alternative pathway, leading to the opsonization of pathogens, recruitment of inflammatory cells, and eventual lysis of the target cells.

Structure and Function

Complement factor D is synthesized as a single chain polypeptide that is secreted by adipocytes, macrophages, and other cell types. The active enzyme is a highly specific serine protease that cleaves Factor B. Its activity is tightly regulated by the availability of its substrate, C3bB, ensuring that the complement system is activated only in the presence of pathogens.

Genetics

The gene encoding complement factor D is located on chromosome 19 in humans. Mutations in this gene can lead to deficiencies in the complement system, which may result in increased susceptibility to infections and certain autoimmune diseases.

Clinical Significance

Alterations in the activity or concentration of complement factor D can have significant clinical implications. Deficiencies in complement factor D are rare but can lead to an increased risk of bacterial infections, particularly with encapsulated bacteria. Conversely, excessive activation of the complement system, which can occur due to high levels of complement factor D, is implicated in various autoimmune diseases, such as atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD).

In recent years, complement factor D has become a target for therapeutic intervention in diseases associated with dysregulation of the complement system. Inhibitors of complement factor D are being developed as potential treatments for conditions like aHUS, AMD, and other complement-mediated diseases.

Research Directions

Research on complement factor D continues to uncover its roles beyond the traditional boundaries of the immune system. Studies have suggested its involvement in metabolic pathways, indicating a broader physiological significance. The development of specific inhibitors and modulators of complement factor D activity holds promise for novel therapeutic approaches to treat a wide range of diseases.