Immune Regulation by C1 esterase inhibitor

Project leaders: Sacha Zeerleder PhD, Diana Wouters PhD and Prof Marieke van Ham PhD

C1 esterase inhibitor (C1-Inh) is an inhibitor of the complement system and the contact system of coagulation. Hereditary angio-edema (HAE), a disease characterized by recurrent attacks of edema, is caused by heterozygous C1-Inh deficiency. C1-Inh preparations purified from plasma have been used for HAE treatment. In collaboration with Sanquin Plasma Products and Viropharma we are exploring possible new fields of clinical application for C1-Inh and are investigating the function of C1-Inh in more detail. In collaboration with prof Hans Niessen (Dept. of Pathology, VUmc) we demonstrated that in diseased aortic valves activated complement is more present than C1-Inh, which gives rise to the question if exogenous addition of C1-Inh might be useful for treatment of this disease. In addition, we are investigating the role of C1-Inh in early vein graft remodeling.

Key publication

• Ter Weeme M, Vonk AB, Kupreishvili K, van Ham M, Zeerleder S, Wouters D, Stooker W, Eijsman L, Van Hinsbergh VW, Krijnen PA, Niessen HW. Activated complement is more extensively present in diseased aortic valves than naturally occurring complement inhibitors: a sign of ongoing inflammation. Eur J Clin Invest 2010; 40:4.