Advances in pemphigus and its endemic pemphigus foliaceus (Fogo Selvagem) phenotype: A paradigm of human autoimmunity

Abstract

Pemphigus encompasses a group of organ specific, antibody mediated autoimmune diseases of the skin characterized by keratinocyte detachment that leads to the development of blisters and erosions, which can become life-threatening. The pathogenic autoantibodies recognize desmogleins, which are members of the desmosomal cadherin family of cell adhesion molecules. Desmoglein 3 is targeted in pemphigus vulgaris while desmoglein 1 is targeted in pemphigus foliaceus and its endemic form, fogo selvagem. This review will briefly define the salient features of pemphigus and the proposed steps in pathogenesis. We will then summarize the most recent advances in three important areas of investigation: (i) epidemiologic, genetic, and immunologic features of fogo selvagem, (ii) molecular mechanisms of injury to the epidermis, and (iii) novel therapeutic strategies targeting specific steps in disease pathogenesis. The advances in each of these three seemingly separate areas contribute to the overall understanding of the pemphigus disease model. These recent advancements also underscore the dynamic interplay between the treatment of patients in a clinical setting and basic science research, which has led to an integrative understanding disease pathogenesis and treatment and allow pemphigus to serve as a paradigm of human autoimmunity.

An Insight into the Sialotranscriptome of Triatoma matogrossensis, a Kissing Bug Associated with Fogo Selvagem in South America

“…2 Endemic pemphigus foliaceus (PF), also known as fogo selvagem (FS) in Brazil, is a human organ-specific autoimmune disease of the skin characterized by skin blistering and pathogenic autoantibodies against desmoglein 1 (Dsg1). 7,8 Dsg1 is an epidermal desmosomal molecule and member of the cadherin family of Ca ++ -dependent cell adhesion molecules. 9 The anti-Dsg1 autoantibodies in FS are immunoglobulin G4 (IgG4) restricted and reproduced the human disease when passively transferred into experimental animals.…”

Pênfigo Foliáceo Endêmico (Fogo Selvagem) e sua associação com fatores ambientais e ocupacionais em Ouro Preto, Minas Gerais, Brasil

“…Enquanto o pênfigo foliáceo apresenta autoanticorpos contra desmogleína1 (anti-dsg1) 4,5 , o pênfigo vulgar caracteriza-se pela presença de anticorpo antidesmogleína 3 (anti-dsg3) na forma mucosa e de anti-dsg1 e 3 na forma mucocutânea 3,6 . O pênfigo foliáceo (PF) pode ser subdividido em clássico ou doença de Cazenave, e endêmico ou fogo selvagem (PFE), cuja endemicidade está presente no Brasil, entre as longitudes 45° e 60° oeste e latitudes 5° e 25° sul, em altitudes que variam entre 500 e 800 metros 7 .…”

Profile of Trypanosoma cruzi Reactivity in a Population at High Risk for Endemic Pemphigus Foliaceus (Fogo Selvagem)

“…[1][2][3][4] There are two main forms of PF: the classic one, with universal distribution, and the endemic form, also known as Fogo Selvagem (FS), prevalent in certain regions of Brazil and other Latin American countries. 1,5 Main differences between the classic and the endemic presentation include peculiar epidemiological features, which are unique to FS, such as the presence of familial cases, involvement of children and young adults, and specific endemic settlements. 6 The peak of FS in Brazil occurred in the first half of the 20th century.…”

“…A Brazilian Amerindian Terena reservation, located at Limao Verde, Aquidauana, State of Mato Grosso do Sul (MS), with a high prevalence of FS (3%), has been closely followed up, once its main features includes a geographic, limited distribution of FS cases, that exhibit familial and temporal clustering. 5,[15][16][17] The immune response in FS is characterized by pathogenic IgG4 auto-antibodies that are driven to the extracellular 1 and 2 domains of Dsg1 (EC1-2). 18 Interestingly, 55% of healthy individuals living in endemic FS areas generate antiDsg1 antibodies that recognize the extracellular 5 domain of Dsg1 (EC-5), a nonpathogenic epitope of the molecule.…”