Tunisian endemic pemphigus foliaceus is associated with desmoglein 1 gene polymorphism

Abstract

Desmoglein 1 is the target antigen and probably the initiating immunogen of the autoantibody response in pemphigus foliaceus (PF),Pemphigus foliaceus (PF) is an autoimmune blistering skin disease characterized by superficial epidermal blisters and the production of pathogenic autoantibodies directed against desmoglein 1, a 160-kDa transmembrane desmosomal glycoprotein belonging to the cadherin superfamily. 1 Two different varieties of PF have been identified. The sporadic form occurs in western Europe and North America with a low incidence (Ͻ1 case per million per year) and equally affects males and females over 50 years old. 2 The endemic form is observed in different geographic regions particularly in Brazil and Tunisia, and has different epidemiological characteristics. 3 In Brazil, PF is known as folgo selvagem (FS), has a high incidence (25 cases per million per year) and predominantly affects young adults with no sex predominance. In Tunisia, PF is mainly observed in females р35 years old, among which the incidence rate reaches 15 cases per million per year. 2,3 Patients with sporadic or endemic PF synthesize autoantibodies with similar immunochemical properties and frequently bear the same HLA class II alleles (DRB1*0102 and DRB1*0404), 4,5 which suggests that common susceptibility loci interact with different environmental factors to cause similar clinical manifestations.

Dermatopathology in sub‐Saharan Africa: a systematic 5‐year analysis of all histopathological diagnoses from the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania

“…Autoimmune bullous skin diseases were unexpectedly relatively frequent representing up to 5% of all histological diagnoses every year. Since most of the affected patients live in the area of the Mount Kilimanjaro and because of clinical and epidemiological peculiarities we have a suspect that they may have an endemic type of pemphigus foliaceus, as found in North Africa …”

Pemphigus foliaceus and desmoglein 1 gene polymorphism: Is there any relationship?

“…In spite of the structural variation of the protein, resulting from the exon 11 polymorphism, the lack of association in all three populations thus far analyzed (French, Tunisian and Brazilian; Martel et al [6], Ayed et al [7] and this study, respectively) allows to conclude that the structural variation in the EA domain plays no role in differential susceptibility to pemphigus foliaceus. Interestingly, anti-EA antibodies are common in individuals without skin disease living in endemic areas [17].…”

“…We conclude that the analyzed genetic variability of the autoantigen dsg1 is not a critical factor modulating susceptibility to this disease. Nevertheless, it should be noticed that there is a consistent tendency towards a higher frequency of variant 809 C and of C/C homozygotes in pemphigus patients, in all three populations analyzed [for genotype C/C, French: OR Z 2.9, P Z 0.03 [8]; Tunisian: OR Z 1.7, P Z 0.046 [7]; Brazilian, this study: OR Z 1.5, P Z 0.078]. Whether this reflects a real slight influence of desmoglein 1 genetic variability on disease susceptibility remains to be proven.…”

“…In contrast to the haplotype signed by the 1660 SNP, the 809 SNP does not result in structural variation of the dsg1 protein. Interestingly, (weak) association between the variants of this SNP and PF were seen in French and in Tunisians [6,7]. Synonymous substitutions do not alter the primary structure of the protein but they must not be silent.…”

Sporadic pemphigus foliaceus and class II human leucocyte antigen allele associations in the white British and Indo-Asian populations in the UK

“…Genetic studies to date have identified associations between PF and the class II major histocompatibility class (MHC) genes encoding for human leucocyte antigen (HLA)‐DR and HLA‐DQ, as well as Dsg1 and some cytokines, notably interleukins (IL)‐4 and IL‐6 . Population association studies with HLA‐DR and HLA‐DQ antigens have been conducted in both endemic and sporadic PF .…”