IDENTIFICATION OF VARIABLES CAUSING DIFFERENT CLINICAL EXPRESSION OF THE INHERITED C1-INHIBITOR DEFICIENCY (HEREDITARY ANGIOEDEMA)

Hereditary angioedema (HAE) is a disease due to the deficiency of C1-inhibitor (C!-INH. It leads to episodic swelling causing deformation of the cutaneous sites (face, hands etc.), severe abdominal pain, and glottis occlusion with death for asphyxia. The severity of the disease is unpredictably variable from subject to subject, but also within the same subject from time to time. There are drugs that effectively prevent symptoms, but these drugs have to be given continuously with important risks. The unpredictability of disease severity renders very difficult the therapeutic decisions. The study is aimed to identify the variables responsible for the severity of HAE. The results will also provide general information on the serine protease inhibitor (serpin), the protein family to which C1-INH belongs. Defects in these proteins lead to different diseases, collectively identified as “conformational diseases”. Among them there are some forms of dementia as Alzheimer and spongiform encephalopaties. Thus the results of this research will benefit HAE patients as well as those patients suffering from diseases in which serpin are involved. The benefits will be better tools for prognosis and treatment monitoring, and targets for new therapeutic approaches.