RELEVANCE OF LYMPHOPROLIFERATIVE DISORDERS AND OF ANTI-C1 INHIBITOR AUTOANTIBODIES IN ACQUIRED ANGIO-EDEMA

We looked for autoantibodies to C1 inhibitor (C1-INH) and evaluated th e relationship of their presence to the associated lymphoproliferative diseases and to the cleaved form of C1-INH in 13 patients with acquir ed C1-INH deficiency (acquired angio-oedema (AAE)). At the time of man ifestation of angio-oedema symptoms or within a few years the followin g diseases were diagnosed: liver angioma (n = 1), M-components (n = 7, one of whom also had echinococcal liver cysts), breast cancer (it = 1 ), chronic lymphocytic leukaemia (CLL; n = 1); three patients had no a ssociated disease. Anti-Cl-INH autoantibodies, measured both as immuno globulin 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-se parated plasma demonstrated that CI-INH circulated in the cleaved 96-k D form in the 12 patients with autoantibodies, but not in the one with out. In conclusion, the large majority of our patients have autoantibo dies to C1-INH. Circulating autoantibodies are necessary for the gener ation of cleaved C1-INH. The paraproteins associated with AAE are freq uently autoantibodies to C1-INH and thus account for its consumption.