The prevalence of antibodies against desmoglein 1 in endemic pemphigus foliaceous in Brazil

Background - Pemphigus foliaceus is an autoimmune skin disease mediated by autoantibodies against desmoglein 1. The endemic form is thought to ahve an environmental cause. The Terena reservation of Limao Verde in Mato Grosso do Sul, Brazil, is a recently identifies focus of the disease, with a prevalence of 3.4 percent in the population. We tested the hypothesis taht normal subjects living in an endemic area have antibodies agaisnt desmoglein 1. Methods - We used an enzyme-linked immunosorbent assay to defect antibodies agaisnt desmoglein 1 in serum samples from 60 patients with endemic pemphigus foliaceus (fogo selvagem) who lived in Limao Verde or elsewhere in Brazil, 372 normal subjects (without pemphigus foliaceus) from Limao Verde and surrounding location, and 126 normal subjects from the United States and Japan. Results - Antibodies against desmoglein 1 were detected in 59 of the 60 patients with fogo selvagem (98 percent) but in only 3 of the 126 normal subjects from the United States and Japan (2 percent). Antibodies were also detected in 51 of the 93 normal subjects from Limao Verde (55 percent) and in 54 of the 279 normal subjects from surrounding areas (19 percent). Serum samples obtained one to four years before the onset of disease were available for five patients; all five had antibodies in the initial serum serumsamples, and the onset of disease was associated with a marked increase in antibody values. Conclusions - The prevalence of antibodies against desmoglein 1 is high among normal subjects living in an area where fogo selvagem is endemic, and the onset of the disease is preceded by a sustained antibody response. These findings support the concept that the production of antibodies against desmoglein 1 is initiated by exporure to an unknown environmental agent

Desmoglein-1-specific T lymphocytes from patients with endemic pemphigus foliaceus (fogo selvagem)

Fogo selvagem (FS), the endemic form of pemphigus foliaceus, is a cutaneous autoimmune disease characterized by subcorneal blistering of the epidermis and the production of autoantibodies against the desmosomal antigen desmoglein-1 (dsg1). Previously, we showed that reproduces the clinical, histological, and immunological features of FS, indicating that autoantibodies play an essential role in the development of this disease. The purpose of this study was to characterize the autoimmune T-cell responseassociated with FS. We provide here the first evidence, to our knowledge, that the great majority of Fs patients have circulating T lymphocytes that specifically proliferate in response to the extracellular domain of Dsg1. Long-term T cells developed from these patients also responded to Dsg1-reactive FS T cells exhibited a CD4-positive memory T-cell phenotype and produced a T helper 2like cytokine profile. These findings represent the initial steps in defining the reloe of T cells in FS autoimmunity