Increased amounts of C4-containing immune complexes and inefficient activation of C3 and the terminal complement pathway in a patient with homozygous C2 deficiency and systemic lupus erythematosus

Plasma and serum samples from a patient with homozygous C2 deficiency and severe systemic lupus erythematosus who responded with full clinical remission after plasma infusions were examined for immune complexes (IC), C3 activation products, and the terminal complement complex (TCC). Plasma contained large amounts of C4-containing IC but no C3-containing IC or complement activation products. Classical pathway activation in vitro did not lead to C3 activation or TCC formation as seen in normal serum, but a very efficient binding of C1q and C4 was found. No disturbances in alternative pathway activation were observed. The results indicate an impaired formation of C3-containing IC and an inefficient clearance of C4-containing IC, supporting the idea of a causal relationship between the dysfunctional classical pathway, pathophysiology, and clinical manifestations in this patient.