Association of specific amino acid sequence (QRRAA) of HLA-DRB1*0405 with rheumatoid arthritis in a Tunisian population.

This study aimed to investigate HLA-DRB1 alleles in rheumatoid arthritis (RA) patients from Tunisia and to examine the effect of these alleles on disease severity. HLA-DRBI alleles and sub-typing of DRBI*04 and *01 were determined in 90 patients and 100 healthy controls, by PCR-SSP. HLA-DRB1*04 was significantly higher in patients (51.1%) than in controls (27%) [OR=2.83, p=0.00066]. DRBJ*0405 was found to be the unique DR4 allele associated with RA (28.88% vs 6%) [OR=6.36, p=0.000059]. A significant decrease in the frequency of HLA-DRB1*0701 was observed in RA patients (16.66%) compared to controls (36%) [p=0.0026]. However, the frequency of patients carrying the shared epitope (SE) QRRAA, was slightly increased compared with controls (37.8% vs 23%) [OR=2.03, p=0.039]. We found that the presence of rheumatoid factor, HLA-DR4 and HLA-DRBI*0405 were not significantly associated with bone erosions or the presence of extra-joint involvement. In our population, the SE (QRRAA) expressed in DRBI*04 alleles is related to the susceptibility to RA but it is not involved in RA severity in Tunisia, while DRBI*0701 might protect against this disease.

Functional polymorphisms of PTPN22 and FcgR genes in Tunisian patients with rheumatoid arthritis.

To investigate a possible association between functional polymorphisms of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22-R620W) and receptors for the Fc fragment of IgG (FcgRIIa-H131R, FcgRIIIa-F158V FcgRIIIb-NA1/NA2), and rheumatoid arthritis (RA), 133 Tunisian patients with RA and 100 controls were genotyped. We found strong evidence of an association of PTPN22 620W allele and RA. However, analysis does not detect an association between auto-antibodies seropositivity, presence of nodules or erosions and this allele. No significant skewing of any of the three FcgR polymorphisms was seen in this RA group. Nevertheless, we identified FcgRIIIa-V/V158 as the most important FcgR genotype for severe disease subset with joint erosions and observed that patients with FcgRIIIb-NA2/NA2 genotype had an earlier incidence of clinical symptoms. In conclusion, we have confirmed that PTPN22 620W allele is associated with Tunisian RA but does not constitute a factor influencing clinical manifestations. Conversely, this study supports that the FcgRIIa/IIIa and IIIb polymorphisms could influence the course and the severity of this disease. A large number of samples are required to provide independent confirmation of these findings.