Transplacental passage of maternal pemphigus foliaceus autoantibodies induces neonatal pemphigus.

The association of maternal pemphigus foliaceus (PF) with neonatal PF is rare and may be secondary to transplacental passage of PF autoantibodies. We describe a 25-year-old patient with PF who was delivered of two consecutive babies, one with classic skin lesions of PF and another that was normal. The neonate with PF was born when the mother had widespread skin disease; the normal newborn was born when the mother was in partial remission. The titers of PF autoantibodies were higher in the mother's serum and the cord serum of the baby with PF than in the mother during partial remission and the unaffected baby. The mother and affected baby had autoantibodies to desmoglein 1. Furthermore, cord blood from the baby with PF induced skin disease when injected into mice. In this case, maternal PF was associated with neonatal PF when the titers of maternal anti-desmoglein 1 autoantibodies were elevated. The cutaneous disease in neonatal PF is due to anti-desmoglein 1 autoantibodies.

The expression and localization of Scl-70/DNA topoisomerase I vary throughout the cell cycle.

PURPOSE AND METHODS: We investigated the expression and localization of topoisomerase I by Western blot and indirect fluorescent antibody assay, respectively, using anti-Scl-70/topo I from patients with diffuse scleroderma. The contribution of topoisomerase I to DNA replication was assessed using cells treated with the topoisomerase I inhibitor camptothecin. RESULTS: Scl-topo I was detected at all cell cycle phases as a single immunoreactive band of 100 kDa. Extracts from cells in the S phase contained the largest amount of immunoreactive Scl-70/topo I. Variations in the subcellular distribution of Scl-70/topo I were seen throughout the cell cycle, with a speckled nucleoplasmic distribution during G1 contrasting with concentration within the nucleolus during S. Camptothecin exposure blocked topoisomerase I expression and caused a significant decrease in DNA production. CONCLUSION: These data suggest (1) that topomerase I is active mainly during the S phase and contributes to DNA replication, and (2) that topoisomerase I may be involved in ribosomal gene transcription.

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 of these studies was to determine the specificity of the autoantibody response in these patients. All patients had clinical and histologic evidence of pemphigus vulgaris. Fogo selvagem sera (n = 8), bullous pemphigoid sera (n = 8), antinuclear antibodies positive sera from patients with lupus erythematosus (n = 2), and normal human sera (n = 8) were used as controls. All pemphigus vulgaris patients showed titers of IgG autoantibodies by indirect immunofluorescence > or = 1:60, predominantly of the IgG4 subclass and immunoprecipitated recombinant desmoglein 3 expressed in the baculovirus system. Patients with disease localized to the mucous membranes showed no reactivity with desmoglein 1 and only one had weak reactivity with mouse skin by indirect immunofluorescence (titer = 1:20). Sera of four of these mucosal patients were tested in the mouse model and three of four did not elicit 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 anti-desmoglein 3 antibodies to a disorder involving mucosas and skin. This transition was associated with the appearance of anti-desmoglein 1 antibodies in the patient's serum. These studies indicate that the autoantibody response in pemphigus vulgaris is heterogeneous. Epitopes recognized by some pemphigus vulgaris sera are species specific and others may be mucosal specific.