MUCOSAL AND MUCOCUTANEOUS (GENERALIZED) PEMPHIGUS-VULGARIS SHOW DISTINCT AUTOANTIBODY PROFILES

Pemphigus vulgaris is an autoimmune bullous disorder characterized by autoantibodies directed against desmoglein 3. A group of 19 pemphigus vulgaris sera were characterized by immunoblotting, immunofluorescence , immunoprecipitation, and the passive transfer mouse model. The aim o f these studies was to determine the specificity of the autoantibody r esponse in these patients. All patients had clinical and histologic ev idence of pemphigus vulgaris. Fogo selvagem sera (n = 8), bullous pemp higoid sera (n = 8), antinuclear antibodies positive sera from patient s with lupus erythematosus (n = 2), and normal human sera (n = 8) were used as controls. All pemphigus vulgaris patients showed titers of Ig G autoantibodies by indirect immunofluorescence greater than or equal to 1:160, predominantly of the IgG4 subclass and immunoprecipitated re combinant desmoglein 3 expressed in the baculovirus system. Patients w ith disease localized to the mucous membranes showed no reactivity wit h desmoglein 1 and only one had weak reactivity with mouse skin by ind irect immunofluorescence (titer = 1:20). Sera of four of these mucosal patients were tested in the mouse model and three of four did not eli cit skin or mucosal disease in the animals. In contrast, sera from all seven patients with disease involving the skin and mucous membranes ( generalized disease) produced disease in neonatal mice. In one patient the disease evolved from pure mucosal involvement associated with ant i-desmoglein 3 antibodies to a disorder involving mucosas and skin. Th is transition was associated with the appearance of anti-desmoglein 1 antibodies in the patient's serum. These studies indicate that the aut oantibody response in pemphigus vulgaris is heterogeneous. Epitopes re cognized by some pemphigus vulgaris sera are species specific and othe rs may be mucosal specific.