Acquired CI-inhibitor deficiency in essential cryoglobulinemia and macrocryoglobulinemia

In 5 patients with mixed cryoglobulinemia, 3 with Waldenström’s disease and 2 with essential cryoglobulinemia, a Cl-inhibitor (CI-INH) deficiency was discovered. The complement profile was characteristic of the acquired type: The total hemolytic activity and the early components were reduced, C3 was diminished in 1 patient only, C5 and C9 were normal or elevated. 1 patient with Waldenstrom’s disease and 1 with essential cryoglobulinemia experienced episodes of angioedema. Circulating immune complexes were found in all patients’ sera by the 12!I-radio-labelled Clq binding activity (Clq BA) test. The values of the Clq binding activity were correlated with the depletion of the early complement components and that of CI-INH. 4 patients showed circulating 7S IgM. Our data support the hypothesis of a complement activation by the cryoprecipitating immune complexes; the CI-INH depletion is secondary to its consumption following Cl activation.