Influence of TNF and IL17 Gene Polymorphisms on the Spondyloarthritis Immunopathogenesis, Regardless of HLA-B27, in a Brazilian Population.

BACKGROUND AND OBJECTIVES: Spondyloarthritis (SpA) represents a heterogeneous group of immune-mediated inflammatory diseases that have overlapping clinical features, genetic predisposition, and pathogenic mechanisms. Hence, we investigated, through a case-control study, whether single-nucleotide polymorphisms of TNF and IL17 genes are associated with SpA, ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in a mixed Brazilian population. METHODS: Genotyping of TNF-308 (rs1800629), TNF-238 (rs361525), IL17A (rs2275913), IL17F (rs763780), and HLA-B27 polymorphisms was performed in 243 patients with SpA and 210 controls from Southern Brazil using SSOP-Luminex (One Lambda) and PCR-SSP assays. RESULTS: Significant associations were confirmed between the HLA-B27 marker and SpA, AS, and PsA diseases. While TNF-308 (rs1800629) AA/GA, IL17A (rs2275913) AA/GA, and IL17F (rs763780) CC/TC genotype frequencies were associated, in the dominance inheritance model, with SpA and AS, regardless of gender, the presence of HLA-B27, TNF-238 (rs361525) GA/AA, IL17A (rs2275913) AA/GA, and IL17F (rs763780) genotypes was associated with PsA. CONCLUSION: In this Brazilian population, TNF and IL17 gene polymorphisms responsible for the expression of important inflammatory cytokines were associated with overall SpA, and, specifically, with AS and PsA, regardless of gender and HLA-B27. However, future larger studies with different ethnicities may be necessary to confirm these genetic associations.

Genetic Polymorphisms of Toll-like receptors 2 and 9 as Susceptibility Factors for the Development of Ankylosing Spondylitis and Psoriatic Arthritis.

INTRODUCTION: Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are classified as spondyloarthritis (SpA), a group of inflammatory rheumatic diseases with complex genetic etiology. Toll-like receptors (TLRs) have an important role in the mechanism of innate immunity and may influence inflammatory responses. Polymorphisms in TLR genes that lead to changes in these receptors or that interfere with the transcription rates of mRNA TLR may be involved in the chronic inflammatory immune response observed in SpA. Currently, there is a lack of studies associating genetic polymorphisms in TLRs and SpA. OBJECTIVE: Therefore, this case-control study is aimed at analyzing the influence of the respective SNPs on TLR2 rs5743708, TLR6 rs5743810, and TLR9 rs5743836 and rs187084 in the immunopathogenesis of SpA. METHODS: The polymorphisms genotyped by PCR-RFLP were TLR2 rs5743708, TLR6 rs5743810, and TLR9 rs5743836 and rs187084. The HLA-B ∗ 27 was performed by PCR-SSP. RESULTS: Logistic regression analysis showed a strong association between SNPs in TLR2 and TLR9 and susceptibility to SpA (OR = 12.56; CI = 6.5-25.9 and OR = 1.62; CI = 1.20-2.21, respectively). No association was observed among HLA-B ∗ 27 and TLR polymorphisms (p = 0.72), nor among BASDAI and TLR polymorphisms (p = 0.85). DISCUSSION: Our findings suggest that polymorphisms in TLR2 and TLR9 genes may contribute to the immunopathogenesis of the SpA. The rs187084, rs5743836, and rs5743708 polymorphisms were associated with the risk of SpA development, in this study, and lead to significant changes in the innate and adaptive immune response profile, as well as the maintenance of the regulation of immunological mechanisms. CONCLUSION: The polymorphism rs5743708 for the TLR2 and the rs187084_rs5743836 TLR9 haplotypes appear to be involved in the development of clinical forms of SpA and can be a possible therapeutic target for the spondyloarthritis.