title: The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity.
abstract: Several clinical and biological features of lymphoproliferative diseases have been associated with an increased risk of developing autoimmune manifestations. Acquired deficiency of C1-inhibitor (C1-INH) (AAE) is a rare syndrome clinically similar to hereditary angioedema (HAE) characterized by local increase in vascular permeability (angioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. Bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein (a serine protease controlled by C1-INH), is the mediator of symptoms. In total 46% of AAE patients carry an underlying hematological disorder including monoclonal gammopathy of uncertain significance (MGUS) or B cell malignancies. However, 74% of AAE patients have anti-C1-INH autoantibodies without hematological, clinical or instrumental evidence of lymphoproliferative disease. Unlike HAE patients, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hypercatabolism of C1-INH. Experiments show that C1-INH and/or the classical complement pathway were consumed by the neoplastic lymphatic tissues and/or anti-C1-INH neutralizing autoantibodies. Therapy of AAE follows two directions: 1) prevention/reversal of the symptoms of angioedema; and 2) treatment of the associated disease. Different forms of B cell disorders coexist and/or evolve into each other in AAE and seem to be dominated by an altered control of B cell proliferation, thus AAE represents an example of the strict link between autoimmunity and lymphoproliferation.
authors.forename: Maddalena Alessandra
authors.initials: MA
authors.lastname: Wu
authors.forename: Roberto
authors.initials: R
authors.lastname: Castelli
mesh_terms: D000799:Angioedema / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D054179:Angioedemas, Hereditary / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001920:Bradykinin / Q000378:metabolism; D003174:Complement C1 Inactivator Proteins / Q000627:therapeutic use; D050718:Complement C1 Inhibitor Protein / Q000276:immunology / Q000378:metabolism; D016208:Databases, Factual; D006801:Humans
chemical_list: D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human; D001920:Bradykinin