title: Relevance of lymphoproliferative disorders and of anti-C1 inhibitor autoantibodies in acquired angio-oedema.
abstract: We looked for autoantibodies to C1 inhibitor (C1-INH) and evaluated the relationship of their presence to the associated lymphoproliferative diseases and to the cleaved form of C1-INH in 13 patients with acquired C1-INH deficiency (acquired angio-oedema (AAE)). At the time of manifestation of angio-oedema symptoms or within a few years the following diseases were diagnosed: liver angioma (n = 1), M-components (n = 7, one of whom also had echinococcal liver cysts), breast cancer (n = 1), chronic lymphocytic leukaemia (CLL; n = 1); three patients had no associated disease. Anti-C1-INH autoantibodies, measured both as immunoglobulin binding to C1-INH immobilized onto microtitre plates (ELISA) and as plasma inhibitory activity of C1-INH function, were found in 12 patients. Binding of C1-INH to paraproteins, transferred to Immobilon after agarose gel electrophoresis, was detectable in five of seven M-components associated with AAE. Immunoblotting analysis of SDS-PAGE-separated plasma demonstrated that C1-INH circulated in the cleaved 96-kD form in the 12 patients with autoantibodies, but not in the one without. In conclusion, the large majority of our patients have autoantibodies to C1-INH. Circulating autoantibodies are necessary for the generation of cleaved C1-INH. The paraproteins associated with AAE are frequently autoantibodies to C1-INH and thus account for its consumption.
authors.affiliation: Institute of Internal Medicine, University of Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cicardi
authors.forename: A
authors.initials: A
authors.lastname: Beretta
authors.forename: M
authors.initials: M
authors.lastname: Colombo
authors.forename: D
authors.initials: D
authors.lastname: Gioffré
authors.forename: M
authors.initials: M
authors.lastname: Cugno
authors.forename: A
authors.initials: A
authors.lastname: Agostoni
mesh_terms: D000328:Adult; D000368:Aged; D000799:Angioedema / Q000139:chemically induced* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D003174:Complement C1 Inactivator Proteins / Q000276:immunology*; D003181:Complement C4 / Q000276:immunology; D005260:Female; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D001323:Autoantibodies; D003174:Complement C1 Inactivator Proteins; D003181:Complement C4