Complement profile in a C1 inhibitor deficient family.

Area of Science:

• Immunology
• Complement System
• Hereditary Angioedema

Background:

• C1 inhibitor (C1INH) deficiency is a rare genetic disorder.
• Patients often experience recurrent angioedema and may develop systemic lupus erythematosus (SLE)-like symptoms.
• The role of complement anaphylatoxins (C3a, C4a) in the pathogenesis is not fully understood.

Purpose of the Study:

• To investigate complement component and anaphylatoxin levels in a family with C1 inhibitor deficiency.
• To evaluate the therapeutic effect of danazol on clinical symptoms and complement abnormalities.
• To assess the C1 inhibitor protein's structure and function before and after danazol treatment.

Main Methods:

• Analysis of complement components (CH50, C4, C1INH) and anaphylatoxins (C3a, C4a).
• Clinical assessment of angioedema and SLE-like symptoms.
• Two-dimensional immunoelectrophoresis to evaluate C1 inhibitor function and electrophoretic mobility.

Main Results:

• Elevated C4a levels were observed with decreased C1 inhibitor.
• Increased C3a levels were associated with SLE-like symptoms and angioedema attacks.
• Danazol treatment normalized CH50, C1INH, and C4 levels within 10 days and improved clinical symptoms.
• No functional or electrophoretic abnormalities in C1 inhibitor were detected.

Conclusions:

• C3a and C4a play significant roles in the pathogenesis of angioedema and associated SLE-like symptoms in C1 inhibitor deficiency.
• Danazol is an effective treatment for normalizing complement abnormalities and managing clinical manifestations.
• The C1 inhibitor protein itself does not appear to be functionally or structurally abnormal in this condition.