Springer Seminars in Immunopathology

, Volume 27, Issue 3, pp 286–298

C1 inhibitor: molecular and clinical aspects

  • Marco Cicardi
  • Lorenza Zingale
  • Andrea Zanichelli
  • Emanuela Pappalardo
  • Benedetta Cicardi
Original Article

DOI: 10.1007/s00281-005-0001-4

Cite this article as:
Cicardi, M., Zingale, L., Zanichelli, A. et al. Springer Semin Immun (2005) 27: 286. doi:10.1007/s00281-005-0001-4

Abstract

C1 inhibitor (C1-INH) is a serine protease inhibitor (serpins) that inactivates several different proteases in the complement, contact, coagulation, and fibrinolytic systems. By its C-terminal part (serpin domain), characterized by three β-sheets and an exposed mobile reactive loop, C1-INH binds, and blocks the activity of its target proteases. The N-terminal end (nonserpin domain) confers to C1-INH the capacity to bind lipopolysaccharides and E-selectin. Owing to this moiety, C1-INH intervenes in regulation of the inflammatory reaction. The heterozygous deficiency of C1-INH results in hereditary angioedema (HAE). The clinical picture of HAE is characterized by bouts of local increase in vascular permeability. Depending on the affected site, patients suffer from disfiguring subcutaneous edema, abdominal pain, vomiting and/or diarrhoea for edema of the gastrointestinal mucosa, dysphagia, and dysphonia up to asphyxia for edema of the pharynx and larynx. Apart from its genetic deficiency, there are several pathological conditions such as ischemia–reperfusion, septic shock, capillary leak syndrome, and pancreatitis, in which C1-INH has been reported to either play a pathogenic role or be a potential therapeutic tool. These potential applications were identified long ago, but controlled studies have not been performed to confirm pilot experiences. Recombinant C1-INH, produced in transgenic animals, has recently been produced for treatment of HAE, and clinical trials are in progress. We can expect that the introduction of this new product, along with the existing plasma derivative, will renew interest in exploiting C1-INH as a therapeutic agent.

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Marco Cicardi
    • 1
    • 2
  • Lorenza Zingale
    • 1
  • Andrea Zanichelli
    • 1
  • Emanuela Pappalardo
    • 1
  • Benedetta Cicardi
    • 1
  1. 1.Department of Internal Medicine, San Giuseppe HospitalUniversity of MilanMilanItaly
  2. 2.Dipartimento di Medicina Interna, IRCCS Maggiore HospitalUniversity of MilanMilanItaly

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