Hereditary angioedema (HAE) is a rare disease which causes swelling episodes throughout the body, including the airways, gastrointestinal system, and extremities.
Most commonly, HAE is caused by a deficiency in the C1-INH protein. This deficiency causes an overproduction of plasma kallikrein. This increased production increases the levels of a peptide called bradykinin in the body. This peptide dilates the blood vessels, working to regulate blood pressure as well as inflammation.
However, HAE can occur in individuals who have a normal amount of the C1-INH protein. These forms are called nl-C1-INH-HAE and can be the result of an unknown mutation (U-HAE) or a mutation in ANGPT-1, PLG-HAE, FXII-HAE, or KNG1-HAE.
Regardless of the cause of HAE, every form of the disease has similar symptoms.
A New Study
A new study conducted in Italy has recently been published in Allergy. Its aim was to uncover whether or not bradykinin is overproduced in all forms of HAE, even where patients have a normal amount of C1-INH.
In total this trial included 105 nl-C1-INH-HAE patients.
They investigated potential biomarkers by analyzing levels of cHK as well as VEGFs, Angs, and sPLA2, which have all been documented as being excessively present in C1-INH-HAE.
Here are some of their findings-
- U-HAE: Higher amounts of cHK than controls (without using protease inhibitors)
- U-HAE: No differences of cHK (with protease inhibitors)
- FXII-HAE: Significantly higher amounts of cHK than controls (without using protease inhibitors)
- U-HAE: Higher amounts of Ang1, VEGf-C, and VEGF-A
- FXII-HAE: Higher amounts of VEGF-C
- No differences between patients and the controls for levels of Ang2 and sPLA2
- No levels were altered for ANGPT1-HAE
In this study, all types of nl-C1-INH-HAE had reduced control of the kallikrein activity. This indicates that bradykinin is the primary cause of HAE symptoms. It simply has different mechanisms for release in the body.
These researchers discuss that it is important to further study whether or not the different mechanisms should effect treatment strategies.
You can read more about this study here.