Pemphigus foliaceus (PF) and the endemic form Fogo Selvagem(FS)are mediated by pathogenic antibodies to the EC1-2 domains of desmoglein-1. There is a preclinical phase with antibodies to only EC5. Based on geographic ...Pemphigus foliaceus (PF) and the endemic form Fogo Selvagem(FS)are mediated by pathogenic antibodies to the EC1-2 domains of desmoglein-1. There is a preclinical phase with antibodies to only EC5. Based on geographic clustering of cases, FS is thought to have an, as yet unidentified, environmental trigger. In this study we have searched for anti-desmoglein-1 antibodies in sera from parasitic (leishmaniasis, Chagas, and onchocerciasis), and infectious diseases (leprosy and South American (SA) blastomycosis), which are prevalent in the same geographic regions of Brazil as FS. A specific and sensitive desmoglein-1 ELISA detected antibodies in 34 of 41 onchocerciasis (83%), 38 of 88 leishmaniasis (43%), 18 of 31 Chagas disease (58%), 7 of 28 SA blastomycosis (25%), and 14 of 83 leprosy sera (17%). These sera recognized epitopes restricted to the EC5 domain. These findings identify several etiological factors for FS. It is hypothesized that a component of insect vector saliva, rather than the parasite itself may trigger an antibody response to EC-5. In persons with the known HLA susceptibility alleles and living in endemic areas, a response to the EC1-2 domains may subsequently develop by epitope spreading with associated clinical signs of FS.展开更多
Fogo selvagem (FS), the endemic form of pemphigus foliaceus (PF), is an autoimmune blistering disease characterized by autoantibodies against desmoglein 1. The Terena reservation of Limao Verde in Mato Grosso do Sul, ...Fogo selvagem (FS), the endemic form of pemphigus foliaceus (PF), is an autoimmune blistering disease characterized by autoantibodies against desmoglein 1. The Terena reservation of Limao Verde in Mato Grosso do Sul, Brazil, is a previously identified focus of disease. Autoantibodies against desmoglein 3 (Dsg3) have also been detected in sera from patients with FS. In an effort to further characterize the serological, geographical, and clinical epidemiology of the disease, we sought to determine the prevalence of anti-Dsg3 autoantibodies in sera from normal subjects living outside of and in an endemic area using an ELISA. Anti-Dsg3 antibodies were detected in 53 of 146 normal subjects from Limao Verde (36%), and in eight of 140 normal subjects from surrounding areas (6%). A significant trend was observed in the proportion of positive tests relative to distance from the endemic area (P < 0.001). Our seroepidemiological observations support the concept that the likely environmental trigger of the antibody response in FS is located in this endemic area, and that the population at risk to develop FS may also be at risk to develop an endemic form of pemphigus vulgaris as reported by our co-investigators from Brasilia.展开更多
文摘Pemphigus foliaceus (PF) and the endemic form Fogo Selvagem(FS)are mediated by pathogenic antibodies to the EC1-2 domains of desmoglein-1. There is a preclinical phase with antibodies to only EC5. Based on geographic clustering of cases, FS is thought to have an, as yet unidentified, environmental trigger. In this study we have searched for anti-desmoglein-1 antibodies in sera from parasitic (leishmaniasis, Chagas, and onchocerciasis), and infectious diseases (leprosy and South American (SA) blastomycosis), which are prevalent in the same geographic regions of Brazil as FS. A specific and sensitive desmoglein-1 ELISA detected antibodies in 34 of 41 onchocerciasis (83%), 38 of 88 leishmaniasis (43%), 18 of 31 Chagas disease (58%), 7 of 28 SA blastomycosis (25%), and 14 of 83 leprosy sera (17%). These sera recognized epitopes restricted to the EC5 domain. These findings identify several etiological factors for FS. It is hypothesized that a component of insect vector saliva, rather than the parasite itself may trigger an antibody response to EC-5. In persons with the known HLA susceptibility alleles and living in endemic areas, a response to the EC1-2 domains may subsequently develop by epitope spreading with associated clinical signs of FS.
文摘Fogo selvagem (FS), the endemic form of pemphigus foliaceus (PF), is an autoimmune blistering disease characterized by autoantibodies against desmoglein 1. The Terena reservation of Limao Verde in Mato Grosso do Sul, Brazil, is a previously identified focus of disease. Autoantibodies against desmoglein 3 (Dsg3) have also been detected in sera from patients with FS. In an effort to further characterize the serological, geographical, and clinical epidemiology of the disease, we sought to determine the prevalence of anti-Dsg3 autoantibodies in sera from normal subjects living outside of and in an endemic area using an ELISA. Anti-Dsg3 antibodies were detected in 53 of 146 normal subjects from Limao Verde (36%), and in eight of 140 normal subjects from surrounding areas (6%). A significant trend was observed in the proportion of positive tests relative to distance from the endemic area (P < 0.001). Our seroepidemiological observations support the concept that the likely environmental trigger of the antibody response in FS is located in this endemic area, and that the population at risk to develop FS may also be at risk to develop an endemic form of pemphigus vulgaris as reported by our co-investigators from Brasilia.
