Beyond HLA Class I Antigens, HFE Mutations in Recurrent Aphthous Oral Ulcers and Behçet's Disease in The South of Tunisia

Objective:
To establish HLA class I and HFE mutation associations with recurrent aphthous oral ulcers (RAOU) and Behçet disease (BD) in a cohort of Southern Tunisian patients.
Materials (Subjects) and Methods
A total of 232 patients with RAOU and 123 healthy controls (HC) were enrolled in our study. Patients were divided into 2 groups based on the presence (BD+: 62) or not (BD−: 170). In the BD+ group, 28 patients had a severe form. In the (BD-) group, RAOU was isolated in 81 patients, associated with mucocutaneous manifestations in 58 patients and with joint symptoms in 25 patients. We studied HLA class I polymorphism and HFE mutations respectively by complement dependent micro lymphocytotoxicity assay and by PCR-RFLP.
Results:
HLA-B51 was positively associated with BD particularly with severe manifestations. Regarding (BD-) group, no association was detected with HLA class I polymorphism. After stratification to clinical manifestations, the isolated RAOU was negatively associated with HLA-A1 with a difference close to significance (12 (14.81 %) vs 32 (26.02 %) in HC; P=0.06). Furthermore, patients with mucocutaneous features had a higher frequency of HLA-B51 (14 (24.14%) vs 11 (11.37%) in patients without mucocutaneous involvement). Considering HFE mutations, patients with isolated RAOU had a higher frequency of H63D when compared with other subgroups especially after limiting comparison to patients of at least five years of follow up.
Conclusion:
This study showed that unlike BD, RAS was not associated with HLA-B51; Moreover, we suggested that H63D mutation was positively associated with isolated RAOU.



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