The Journal of Clinical Investigation recently published a study regarding hereditary angioedema type III (HAE), a rare and serious genetic disorder characterized by excruciating swellings in the skin and organs. The international team of scientists have revealed that the disorder is caused via a defective blood protein – coagulation factor XII. These findings can potentially improve treatment and management strategies for patients.

Understanding Hereditary Angioedema

Oedema is a condition in which tissues tend to swell due to fluid retention. This common problem occurs in various pathologies, such as kidney diseases and allergies. The swelling is basically a result of fluid that leaks from within blood vessels into the surrounding tissues.

In hereditary angioedema, this leakage and consequent swelling is primarily caused by a hormone known as bradykinin. HAE is a rather serious and painful condition that involves swelling of the skin and regions of the gastrointestinal tract. These episodes can be life-threatening if vital passages, such as the airways, become obstructed or constricted.

HAE has two common variants – HAE type I and II – the causes of which are well-documented. However, HAE type III was discovered recently, and to treat and manage the condition, it is crucial to understand the underlying mechanisms.

Discoveries And Inferences: What Causes Hereditary Angioedema

Dr Jenny Björkqvist at the Department of Molecular Medicine and Surgery, Karolinska Institutet, was among the researchers involved in the study. The team already knew that HAE type III patients have a mutation in coagulation factor XII. However, they did not know exactly what caused the swellings. While determining the possible mechanism, researchers observed that a single sugar was absent from the mutated blood clotting factor, making it overactive and enhancing its expression of bradykinin – underlying cause behind the swelling.

Prognosis

In normal individuals, natural inhibitors in the blood prevent the coagulation factor from over-expressing bradykinin. These inhibitors are capable of binding and inhibiting the mutated factor XII as well, but this process is not sufficient to completely hinder over-activation.

What Causes Hereditary Angioedema

Principal Investigator Dr Thomas Renné at the Department of Molecular Medicine and Surgery, Karolinska Institutet, stated that in order to fully manage and treat HAE, scientists need to find substances that would affectively block the mutated factor XII. “We have previously developed an antibody that can inhibit factor XII, and have demonstrated that this antibody blocks blood clot formation. In this study, we observed that the same agent prevents the occurrence of oedema in mice.”

Researchers anticipate that the results and inferences derived from the study will help in developing effective treatments for HAE type III patients, and may also provide a broader base for treating other diseases involving swelling.