AI Article Synopsis
- The study investigates the role of toll-like receptors (TLRs) in systemic lupus erythematosus (SLE), focusing on genetic polymorphisms and TLR expression in patients.
- It analyzed genetic variations in TLR genes from 143 SLE patients and 432 healthy individuals, revealing significant associations between SLE and specific polymorphisms in TLR3, TLR8, and TLR9.
- Additionally, higher mRNA expression levels of TLR7, TLR8, and related cytokines were found in SLE patients compared to healthy controls, suggesting a link between these TLRs and the disease's development.
Article Abstract
Objectives: Toll-like receptors (TLRs) are pattern-associated receptors in innate immunity that may be involved in the recognition of self-antigens and the production of pathogenic autoantibodies. This study was undertaken to examine whether polymorphisms of TLR genes are associated with SLE and to determine the expression of various TLRs in peripheral blood mononuclear cells (PBMCs) of patients with SLE.
Methods: The TLR polymorphisms in a cohort of 143 Danish lupus patients and 432 healthy Danish blood donors were analysed. Groups were age matched. Genotyping for the TLR single-nucleotide polymorphisms (SNPs) was performed using Sequenom Multiplex technology. In addition, the mRNA expression of TLRs in PBMCs from 56 SLE patients and 56 healthy controls was studies by quantitative real-time PCR.
Results: We found a genetic association with SLE and three SNPs located within the TLR3, TLR8 and TLR9 genes (rs3775291, P = 0.006; rs37648, P = 0.013; rs352143, P < 0.02). Furthermore, the relative TLR7, TLR8, IFN-α and LY6E mRNA expression levels were significantly higher in SLE patients than in healthy controls (P < 0.0001, P < 0.0001, P = 0.0004 and P < 0.0001, respectively).
Conclusion: These results obtained from a female lupus population of Danish ancestry suggest that variations in TLR3, TLR8 and TLR9 genes are implicated in the pathogenesis of the disease. If these polymorphisms are associated with innate immune dysfunction they may add to the growing field of theoretically well founded new therapeutic targets.
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| http://dx.doi.org/10.1093/rheumatology/ket316 | DOI Listing |
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