Evidence for complement activation via the alternate pathway in skin diseases I. Herpes gestationis, systemic lupus erythematosus, and bullous pemphigoid

Abstract

A patient with herpes gestationis, 6 of 6 patients with bullous pemphigoid and 5 of 25 patients with systemic lupus erythematosus were found to have properdin deposited along the skin basement membrane. The patient with herpes gestationis demonstrated by immunofluorescence basement membrane deposition of C3 and C5 in the absence of C1q, immunoglobulins and light chains. A second patient with herpes gestationis had C3 deposition with no demonstrable immunoglobulins or light chains. A thermolabile humoral factor(s) capable of depositing C3 (without C1q or C4) on normal skin basement membrane was found in the sera of both patients with herpes gestationis. No anti basement membrane antibodies could be demonstrated in the sera of these patients. The patients with systemic lupus erythematosus and bullous pemphigoid who manifested properdin deposition also showed skin basement membrane deposits of C1q, C4, C3, C5 and immunoglobulins. C3 proactivator (C3PA) was also found deposited along the skin basement emmbrane in 3 patients with systemic lupus erythematosus and all 6 bullous pemphigoid patients. This study provides suggestive evidence that activation of complement is occurring via the alternate pathway in herpes gestationis. In systemic lupus erythematosus and bullous pemphigoid, both the classical (antibody) mediated activation of complement as well as the alternate pathway may be operative.