Jochem Alsenz

During the past 25 years, three forms of deficiency of the inhibitor of the first component of complement (C1 inhibitor) with angioedema have been recognized; two forms are hereditary and one is acquired. As compared with hereditary angioedema, the syndrome of acquired C1-inhibitor deficiency is rare, and it is usually associated with lymphoproliferative diseases. We report another type of acquired C1-inhibitor deficiency with angioedema. Two patients with recurrent angioedema but no associated diseases were found to have IgG1 autoantibodies against C1 inhibitor. The anti-C1-inhibitor antibodies prevented binding of C1 inhibitor to activated C1s. Both patients had 60 to 70 percent of normal levels of C1 inhibitor, but it was functionally inactive, with a molecular weight of 96,000 (normal C1 inhibitor, 105,000). In vitro studies of the patients' serum revealed degradation of 125I-labeled 105,000-dalton C1 inhibitor into the inactive 96,000-dalton molecule, caused by activated C1s and not found in normal human serum. We conclude that these cases of acquired C1-inhibitor deficiency resulted from a blockade of C1-inhibitor function by the anti-C1-inhibitor antibodies and from subsequent inactivation of C1 inhibitor by the now uncontrolled enzyme, activated C1s. As in other forms of C1-inhibitor deficiency, the unopposed activation of the complement system led to angioedema.