C1-INH in Hereditary Angioedema (HAE)

Learn more about Function of C1 Esterase Inhibitor in the Normal Contact Pathway and The Contact System in Patients with Hereditary Angioedema

Most people make functional C1 Esterase Inhibitor (C1-INH) at normal levels, allowing their own bodies to regulate and limit inflammation, regardless of the cause. However, patients with a disease called Hereditary Angioedema, or ‘HAE,’ have a mutation in the gene for C1-INH.  HAE - also known as C1-INH deficiency - is a swelling disorder that affects approximately 1 in 50,000 individuals in the United States. People who have the C1 INH mutation or HAE have difficulty regulating inflammation and swelling in their bodies.

Although the causes of swelling in HAE patients are not well defined, it is thought that increased vascular permeability and HAE swelling episodes are primarily mediated through the Contact system and bradykinin production. Because HAE patients do not make enough functional C1-INH to halt the mobilization of bradykinin, bradykinin release goes unchecked and fluid release into the tissue can become uncontrolled. In individuals with normal levels of functional C1-INH, bradykinin release can be stopped by C1 INH and swelling in the body is tightly regulated. In patients with HAE, however, these inflammatory elements go unregulated leading to the potentially severe swelling which causes the disfigurement and pain associated with the disease.

C1-INH inhibits proteins in the inflammation system by binding irreversibly to them; though as C1-INH is used up, more has to be produced to keep up with the demand. Unfortunately, patients with HAE cannot produce enough C1-INH to keep up with the demand for functional C1-INH. C1-INH is used by several pathways in the body; when an HAE patient uses up C1-INH in one pathway, the control of other pathways can become vulnerable, which places HAE patients at risk for uncontrolled swelling. Fluid accumulation during an HAE attack causes pain, disfigurement, and a temporary loss of function in the affected body region. Attacks can be life-threatening – for example, attacks which affect the throat can lead to suffocation if not treated.