The syndrome of acquired angioedema and C1-inhibitor deficiency is associated with B-cell lymphoproliferative disease. It is characterized by accelerated consumption of C1q and C1 inhibitor in vivo and by low levels of serum C2 and C4. Four patients with B-cell malignant diseases (IgA myeloma, macroglobulinemia, chronic lymphocytic leukemia, and B-cell lymphoma, respectively) and acquired C1-inhibitor deficiency were found to have circulating antiidiotypic antibodies to the monoclonal immunoglobulin expressed on the surface of their B cells (three patients) or in the cytoplasm of their bone-marrow cells (one patient). Two of the four patients had circulating M components, and their antiidiotypic antibodies reacted with the M components. In three patients studied the percentage of B cells bearing C1q was 18, 24, and 35 per cent, as compared with 2.3±1.7 per cent (mean±S.D.) in six normal controls.

These results suggest that an interaction between the idiotype of monoclonal immunoglobulins and antiidiotypic antibodies causes increased consumption of C1q and C1 inhibitor in patients with acquired angioedema and C1-inhibitor deficiency. We propose that the subsequent activation of the early components of complement leads to increased vascular permeability and to angioedema and that these patients have a disease caused by antiidiotypic antibodies. (N Engl J Med 1985; 312:534–40.)