C1-INH

C1-Inhibitor (C1-INH) is a protein that plays a crucial role in the regulation of the complement system, which is a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear pathogens from an organism. C1-INH is also involved in the coagulation system and the fibrinolytic system, making it a key player in controlling inflammation and maintaining vascular stability.

Function

C1-INH is a serine protease inhibitor (serpin) that primarily inhibits the enzymes C1r and C1s of the complement system's classical pathway, preventing spontaneous activation. By doing so, it regulates the complement system and prevents excessive inflammation that could damage the host tissue. Additionally, C1-INH inhibits factors of the coagulation and fibrinolytic systems, including kallikrein, factor XIIa, and plasmin, which are involved in blood clotting and dissolution, respectively.

Genetic and Molecular Basis

The gene encoding C1-INH is located on chromosome 11 in humans. Mutations in this gene can lead to hereditary angioedema (HAE), a rare genetic disorder characterized by sudden and recurrent episodes of swelling in various parts of the body, including the extremities, face, gastrointestinal tract, and airways.

Clinical Significance

1. 1. 1. Hereditary Angioedema ###

Hereditary angioedema due to C1-INH deficiency is classified into two types: Type I, which is characterized by low levels of C1-INH, and Type II, where the C1-INH is dysfunctional. Both types lead to uncontrolled activation of the complement and contact systems, resulting in increased bradykinin production, which is primarily responsible for the swelling and pain associated with the disease.

1. 1. 1. Acquired C1-INH Deficiency ###

Acquired deficiency of C1-INH is similar to hereditary angioedema but occurs in individuals without a family history of the condition. It is often associated with lymphoproliferative disorders and is believed to be caused by the consumption of C1-INH by abnormal immune complexes or autoantibodies against C1-INH.

Treatment

Treatment for C1-INH deficiency focuses on preventing and managing acute attacks and may include androgens, fibrinolytics, and C1-INH concentrate. For hereditary angioedema, therapies that increase the level of functional C1-INH or inhibit the production of bradykinin can be effective in preventing and treating attacks.

Research Directions

Research in the field of C1-INH is focused on better understanding its role in the immune system and developing new treatments for conditions related to its dysfunction, such as hereditary angioedema. Advances in genetic therapy and biotechnology hold promise for more effective and targeted treatments in the future.