C3 IS ACTIVATED IN HEREDITARY ANGIOEDEMA, AND C1 C1-INHIBITOR COMPLEXES RISE DURING PHYSICAL STRESS IN UNTREATED PATIENTS/

Seven patients with hereditary angioedema (HAE) were studied to unders tand further how physical exercise may induce attacks. The most pronou nced differences between patients and controls, however, were independ ent of the controlled bicycle run (mean values in patients/controls); C4(g/L): 0.12/0.28 (P = 0.0122); C4bc (AU/ml): 137.0/18.0 (P = 0.0002) ; C4d (mg/mL): 5.03/2.35 (P = 0.0004); C3bc (AU/ml): 8.4/6.3 (P = 0.00 49); C3a (AU/ml): 11.1/5.6 (P = 0.0102). The ratio C4bc to C4 was 1141 versus 64. Consequently, a substantial part of the low amount of C4 l eft in HAE patients consists of activation products, and the authors s how for the first time that a mild but significant activation of C3 oc curs in HAE. The two HAE patients treated with danazol had values of C 1-INH function and antigen, C4, and C2 in-between those of normal and untreated patients, and lower levels of split products from C4 and hig h molecular weight kininogen than untreated patients. As a result of t he exercise, fibrinolysis increased significantly in both patients and controls, while C1/C1-INH complexes rose significantly only in the fi ve HAE patients without treatment when compared to the seven controls (P = 0.0089). This study thus suggests that complement activation is e nhanced in untreated HAE patients following physical stress.