Association of HLA Alleles with Primary Sjögren Syndrome in the South Tunisian Population.

OBJECTIVE: In order to investigate human leukocyte antigen (HLA) genes predisposing to primary Sjögren syndrome (pSS), we conducted an association study using HLA loci (A, B, and DRB1) and 9 polymorphic microsatellite markers spanning the HLA region in pSS patients as compared to healthy individuals. SUBJECTS AND METHODS: Forty-four patients fitting the European criteria of pSS and 123 healthy controls were analyzed for their HLA class I and class II alleles. HLA class I typing was performed using a standard microlymphocytotoxicity method followed by PCR-SSP. HLA-DRB1 genotyping was performed using PCR-SSP. We studied the polymorphism of 9 microsatellite markers for both groups. Microsatellite genotyping was performed using the PCR fluorescent technique. RESULTS: We observed a positive association between HLA-B15 and pSS in the Tunisian population (p = 0.004, OR 7.57). The comparison of the frequencies of DRB1 alleles in pSS patients and controls confirmed the association of the DRB1*03 allele with pSS (p = 0.02, OR 2.36). On the other hand, the association study of microsatellite markers showed that the a9 allele of D6S265 marker and the a20 of C1.2.C were found to be positively associated with pSS as compared to controls (p =0.0003, OR 10.29, and p =0.001, OR 4.79, respectively). Using the "Haplo.stats" software analysis, we found that the most associated region was located in the HLA class I region and limited by HLA-A and D6S265 loci (p = 0.00056). CONCLUSION: The results of this study support the hypothesis of the existence of a susceptibility gene for pSS located in the HLA class I and III regions.

HLA Class III: A susceptibility region to systemic lupus erythematosus in Tunisian population.

BACKGROUND AND OBJECTIVES: Short tandem repeats (STR) are usually used as informative polymorphic markers for genetic mapping and for disease susceptibility analysis. The involvement of these microsatellite markers localized in the MHC region was reported in many auto-immune diseases. In this study we analyzed for the first time eight polymorphisms of microsatellite loci at the HLA region: D6S291, D6S273, TNFa, b and c, MICA, D6S265 and D6S276, in Tunisian systemic lupus erythematosus (SLE) patients. MATERIALS AND METHODS: We performed a case control study in which the microsatellite loci were amplified using specific primers labeled with NED, VIC, PET or 6-FAM and analyzed using GeneScan software 3.7. For the statistical analysis, we used SPSS software and we performed a sub-haplotype scoring test using the haplo.stats software developed in the R language. RESULTS: We found that two mean associated regions existed; the most statistically significant encompassed the 3 TNF markers (p = 0.0003, OR = 19.34); the latter covered the DR region. In fact, when scoring haplotypes in 3 marker- sliding windows, the p value increased as we moved away from the TNF region and decreased again when we approached the DRB1 locus. We also established for the first time the negative association between alleles of D6S291 and SLE. The majority of clinical and serological correlations were noted with TNF alleles. CONCLUSION: Our results confirm the association between TNF and DRB1 polymorphisms and SLE. The association between alleles of D6S291 and SLE needs however to be verified by the analysis of other markers beyond this region.

Human leukocyte antigens-DRB1*03 is associated with systemic lupus erythematosus and anti-SSB production in South Tunisia.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease with various presentations. This variation is due to the interaction of hormonal, environmental, and genetic factors. Associations between human leukocyte antigens and SLE have long been recognized in different ethnic populations and have been suggested to represent the most important association. OBJECTIVES: The objectives of this paper were to determine susceptibility and protection human leukocyte antigens (HLA) Class II markers for SLE and to highlight, for the first time, associations between HLA alleles and clinical and serological features in South Tunisia. METHODS: We conducted a case-control study on 75 SLE patients and 123 healthy controls. The HLA Class II DRB1/DQB1 of all patients and controls was genotyped using polymerase chain reaction-sequence specific primer technique. Statistical analysis was performed using SPSS software. RESULTS: HLA-DRB1*03 was the principal Class II allele associated with the genetic susceptibility to SLE (pc = 0.02; OR = 2.57; CI = [1.39-4.75]; this allele was also associated with anti-SSB production (P = 0.016; OR = 4.00; CI = [1.24-12.96]). HLA-DRB1*01 was significantly more expressed in SLE patients with neurologic disorders (P = 0.013; OR = 20.25; CI = [1.87-219.21]). No allele was found to be protective against SLE in our study group. CONCLUSION: Our results show that in South Tunisia SLE is associated with HLA-DRB1*03 and that some clinical features of SLE may be influenced by specific DRB1 and DQB1 alleles.