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  • Title: Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles.
    Author: Abida O, Zitouni M, Kallel-Sellami M, Mahfoudh N, Kammoun A, Ben Ayed M, Masmoudi A, Mokni M, Fezzaa B, Ben Osman A, Kammoun MR, Turki H, Makni H, Gilbert D, Joly P, Tron F, Makni S, Masmoudi H, Franco-Tunisian Group for Survey and Research on Pemphigus.
    Journal: Br J Dermatol; 2009 Sep; 161(3):522-7. PubMed ID: 19486004.
    Abstract:
    BACKGROUND: Pemphigus foliaceus is an autoimmune blistering skin disease that partly results from genetic factors, especially human leucocyte antigen (HLA) class II genes. OBJECTIVES: The aim of the study was to determine the HLA DR/DQ markers of susceptibility and protection in the Tunisian endemic form. METHODS: Genomic DNA from 90 patients with pemphigus foliaceus recruited from all parts of the country and matched by age, sex and geographical origin with 270 healthy individuals, was genotyped. RESULTS: Firstly, when the whole patient population was studied, DRB1*03, DQB1*0302 and DRB1*04 alleles were significantly associated with the disease while a significant decrease of, in particular, DRB1*11 and DQB1*0301 was observed in patients compared with controls. DRB1*0301 was the dominant allele in DR3-positive patients and controls, while DRB1*0402 was found in 42% of DR4-positive patients. Secondly, when the HLA DR/DQ allele distribution was studied after dividing patients according to their geographical origin, the southern group, which consisted exclusively of patients with the endemic form of the disease, showed the same associations as the whole pemphigus foliaceus population, particularly with DRB1*03. In the northern group, only the DRB1*04 and DQB1*0301 alleles were found to be associated. Interestingly, anti-desmoglein 1 antibody-positive healthy controls did not carry susceptibility alleles but, in contrast, most carried negatively associated alleles. CONCLUSIONS: 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.
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