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

Abstract

Background Desmoglein 1 (Dsg1), the pemphigus foliaceus (PF) antigen, is produced as a precursor (preDsg1) and is transported to the cell surface as the mature form (matDsg1). Recent studies show that B cells from North American individuals without pemphigus can potentially produce anti-preDsg1 IgG antibodies, but ELISA screening of large numbers of normal people in North America and Japan hardly ever shows circulating antibodies against preDsg1 or matDsg1. In contrast, in Tunisia, where PF is endemic, anti-Dsg1 IgGs are frequently detected in healthy individuals. Objective To characterize these anti-Dsg1 antibodies from normal individuals in Tunisia. Methods Sera from 16 healthy individuals and 9 PF patients in the endemic PF area in Tunisia, and sera from Japanese non-endemic PF patients were analyzed by immunoprecipitation-immunoblotting using recombinant proteins of preDsg1, matDsg1, and domain-swapped Dsg1/Dsg2 molecules. Results Sera from normal Tunisian individuals reacted to preDsg1 alone (8/16) or more strongly to preDsg1 than to matDsg1 (7/16), while those from all Tunisian PF patients and Japanese non-endemic PF patients reacted similarly to preDsg1 and matDsg1, or preferentially to matDsg1. The epitopes recognized by anti-Dsg1 IgGs from normal Tunisian individuals were more frequently found in the C-terminal extracellular domains (EC3 to EC5), while those in Tunisian endemic PF patients were more widely distributed throughout the extracellular domains, suggesting IgGs against EC1 and EC2 developed during disease progression. Conclusions These findings indicate that IgG autoantibodies against Dsg1 are mostly raised against preDsg1 and/or C-terminal domains of Dsg1 in healthy Tunisians in the endemic area of PF.

Assessment of the quality of life of Egyptian and Tunisian autoimmune bullous diseases’ patients using an Arabic version of the autoimmune bullous disease quality of life and the treatment of autoimmune bullous disease quality of life questionnaires

“…3 An endemic form of those diseases is present in Brazil and Tunisia. 4,5 These diseases are characterized by cutaneous blisters and mucosal erosions. Not only the pain, erosions and disfigurement of those diseases affect the patients' quality of life, but also the inability to work and the financial status add to their burden.…”

Update on immunogenetics of Tunisian endemic pemphigus foliaceus

“…This result suggests that progression from the preclinical to the clinical phase of the disease is closely associated with subclass switching, from IgG2 to IgG4 subclass in the Tunisian population. Furthermore, we have demonstrated, in collaboration with the group of Prof. Masakuchi Amagai (Keio University, Tokyo, Japan), that patients’ anti‐Dsg1 Abs recognize the N‐terminal domains (EC1, EC2, and EC3) of the mature and precursor forms of Dsg1, whereas those of healthy relatives and controls recognize the C‐terminal domains (EC4 and EC5) of the precursor form only …”

Antibodies against Desmoglein 1, Desmoglein 3 and BP180 in Healthy Tunisians Blood Donors without Immunopathological Phenotype

“…The sera of patients and healthy blood donors was evaluated by Indirect Immunofluorescence (IIF) using normal human skin cryosections as previously described [19]. Briefly, human skin cryosections were incubated with serial dilutions (1:10, 1:40, and 1:160) of tested sera for an hour at room temperature or overnight at 48°C.…”

“…Recombinant proteins were produced as previously described using Dsg3 (or Dsg1)/Dsg2 domain-swapped molecules [21]. Immunoprecipitation-immunoblotting analysis was performed to examine the epitopes of anti-Dsg1 and anti-Dsg3 Abs from each group according to previously described [19].…”