Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles

Abida, Olfa; Zitouni, M.; Kallel-Sellami, M.; Mahfoudh, N.; Kammoun, A.; Ayed, M. Ben; Masmoudi, A.; Mokni, M.; Fezzaa, B.; Osman, A. Ben; Kammoun, Mohamed; Turki, H.; Makni, H.; Gilbert, Danièle; Joly, P.; Tron, François; Makni, S.; Masmoudi, Hatem

doi:10.1111/j.1365-2133.2009.09207.x

Cited by 42 publications

(33 citation statements)

References 15 publications

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“…We have previously shown DRB1 ⁄ 03 and DRB1 ⁄ 04 as susceptibility alleles of the Tunisian endemic PF [5]. It is thus questionable if the association, that we found in the current data with the TNFa, is due to a disequilibrium with these HLA class II alleles or it argues for the contribution of this STR polymorphism at the occurrence of PF.…”

Section: Strs and Hla Class II Association Study By Logistic Regressicontrasting

confidence: 73%

“…In fact, in addition to the DRB1 ⁄ 04 and DQB1 ⁄ 03:02 which seem to be common alleles to all forms of PF observed in the world, the DRB1 ⁄ 03 allele can be considered to be the main and characteristic susceptibility allele of the Tunisian endemic PF [5]. The major mechanism proposed to explain the association between HLA genes and autoimmune diseases is that diseaseassociated alleles can efficiently accommodate an auto-antigenderived peptide initiating the autoreactive T-cell response.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms of HLA microsatellite marker in Tunisian pemphigus foliaceus

et al. 2013

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Section: Strs and Hla Class II Association Study By Logistic Regressicontrasting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Polymorphisms of HLA microsatellite marker in Tunisian pemphigus foliaceus

et al. 2013

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“…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).…”

Section: Methodsmentioning

confidence: 99%

“…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]. Anti-Dsg1 antibodies (Abs) have been detected in normal subjects living in an area where PF is endemic [3].…”

Section: Introductionmentioning

confidence: 99%

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

Toumi

Saleh

Yamagami

et al. 2013

Journal of Dermatological Science

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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.

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“…The strong associations with distinct HLA class II alleles reported in both Brazilian and Tunisian EPF patients (Abida et al, 2009) implies that genetic factors influence the development of EPF. In this context, the report by Recently, we isolated several antiDsg3 pathogenic IgG monoclonal antibodies from PV patients.…”

Section: Interplay Of Genetic and Environmental Factors In The Develomentioning

confidence: 98%

Endemic Pemphigus Foliaceus: Towards Understanding Autoimmune Mechanisms of Disease Development

Zenzo

Zambruno

Borradori

2012

Journal of Investigative Dermatology

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Fogo selvagem is an endemic form of pemphigus foliaceus (EPF) found in Brazil. Environmental and genetic factors are thought to contribute to the disease, which is associated with pathogenic IgG4 autoantibodies against the desmosomal cadherin desmoglein 1. In this issue, as an additional framework to understand autoimmune mechanisms in EPF, Flores et al. have investigated whether fogo selvagem patients and healthy individuals from endemic areas develop autoantibody responses against other desmosomal cadherins and E-cadherin.

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Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles

Abstract: These observations indicate that a particular genetic background characterizes the Tunisian endemic form of pemphigus foliaceus and that HLA class II genes control the pathogenic properties of the autoimmune response rather than the initial breakage of B-cell tolerance.

Cited by 42 publications

References 15 publications

Polymorphisms of HLA microsatellite marker in Tunisian pemphigus foliaceus

Polymorphisms of HLA microsatellite marker in Tunisian pemphigus foliaceus

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

Endemic Pemphigus Foliaceus: Towards Understanding Autoimmune Mechanisms of Disease Development

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