Anti-desmoglein 1 antibodies in Tunisian healthy subjects: arguments for the role of environmental factors in the occurrence of Tunisian pemphigus foliaceus

Abstract

SUMMARYPemphigus foliaceus is an autoimmune blistering skin disease mediated by autoantibodies directed against desmoglein 1 and occurs as a sporadic form throughout the world, or as an endemic form called fogo selvagem in Brazil. Healthy subjects living in Brazilian endemic areas produce antidesmoglein 1 antibodies, suggesting the role of environmental factors in the initiation of the autoimmune response. Tunisia was described recently as an endemic area where the disease is characterized by its high rate among young people, especially women. An enzyme-linked immunosorbent assay using recombinant desmoglein 1 as antigen was used to detect antibodies against desmoglein 1 and calibrated with sera from 67 French healthy blood donors, 20 French pemphigus foliaceus patients and patients with other bullous skin diseases. When sera from 179 healthy Tunisian blood donors were tested, 31 (17%) were found positive. The desmoglein 1 binding activity of these 31 sera was confirmed in 10 cases by indirect immunofluorescence analysis and/or immunoblotting using human epidermal extract. Subclass analysis of antidesmoglein 1 antibodies showed that they were almost exclusively of the IgG2 subclass in positive normal sera and of IgG4 subclass in patients with PF. Thus, antibodies against desmoglein 1 are prevalent in normal subjects living in Tunisia which, along with their IgG2 isotype, suggests the role of the environment in the pathogenesis of this endemic type of pemphigus foliaceus and the need for additional factors to switch from a subclinical to a clinical form of the disease.

Antibodies against desmoglein 1 in healthy subjects in endemic and nonendemic areas of pemphigus foliaceus (fogo selvagem) in Peru

“…This is lower than the frequency reported by Warren et al 1 . and higher than the results reported by Kallel Sellami et al 24 . in Tunisia, who found 17% of positive cases.…”

“…Indirect immunofluorescence staining and enzyme‐linked immunosorbent assay (ELISA) are the most important immunologic assays for the detection of antibodies against desmoglein 1 20–23 . ELISA is more sensitive and specific than the conventional indirect immunofluorescence technique 21,24 …”

Autoimmune reactivity against precursor form of desmoglein 1 in healthy Tunisians in the area of endemic pemphigus foliaceus

“…We examined sera from nine Tunisian patients with endemic PF (TPF) and 16 healthy subjects found in previous studies by our group to have anti-Dsg1 Abs [6, 9, 13]. Among these 16 normal subjects, seven were relatives of PF patients (THR) and nine were healthy controls (THC).…”

“…In 1993, the presence of an endemic form of PF in southern Tunisia was reported [4, 5]. Both sporadic and endemic forms are clinically, histologically, and immunologically similar; however, the endemic form has several unique features, such as geographic and familial clustering and high prevalence among young adults [5, 6]. …”

“…Characteristics of the Tunisian endemic form of PF include a significantly higher incidence in southern regions as compared with northern regions [6, 7]. The observation that the majority of PF family cases in Tunisia were also located in the southern regions implies the role of genetic susceptibility or environmental factors, and DRB1*03 was concluded to be the main susceptibility allele for the Tunisian endemic PF in previous studies [8, 9].…”