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. 2013 May 16;1(1):20.
doi: 10.1186/2050-7771-1-20.

Polymorphisms of Toll-like receptor-4 and CD14 in systemic lupus erythematosus and rheumatoid arthritis

Affiliations

Polymorphisms of Toll-like receptor-4 and CD14 in systemic lupus erythematosus and rheumatoid arthritis

Tarak Dhaouadi et al. Biomark Res. .

Abstract

Background: Toll-like receptor 4 (TLR4) and its co-receptor CD14 play a major role in innate immunity by recognizing PAMPs and signal the activation of adaptive responses. These receptors can recognize endogenous ligands mainly auto-antigens. In addition, TLR4 (Asp299Gly) and CD14 (C/T -159) polymorphisms (SNPs) may modify qualitatively and/or quantitatively their expression. Therefore, they could be implied in autoimmune diseases and can influence both susceptibility and severity of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Patients and methods: TLR4 (Asp299Gly) and CD14 (C/T -159) SNPs were genotyped using polymerase chain reaction (PCR)-RFLP in 127 SLE patients, 100 RA patients, and 114 healthy controls matched in age and gender.

Results: CD14*T allele was significantly more frequent in SLE patients (0.456) comparatively to controls (0.355), p = 0.02 OR (95% CI) = 1.53 [1.04-2.24]. In RA patients, the higher frequency of CD14*T allele (0.405) failed to reach significance, p = 0.28. Investigation of the TLR4 (Asp299Gly) SNP showed no significant association neither with SLE nor with RA.Analysis of these SNPs according to clinical and biological features showed a significant higher frequency of arthritis in SLE patients carrying CD14*T/T genotype (92%) comparatively to those with C/C and C/T genotypes (72.5%), p = 0.04. Moreover, SLE patients carrying CD14*T/T/TLR4*A/A haplotype had significantly more arthritis (91.3%) than the rest of SLE group (73%), p = 0,044 and confirmed by multivariable analysis after adjustment according to age and gender, p = 0.01.

Conclusion: The CD14 (-159)*T allele seems to be associated with susceptibility to SLE and arthritis occurrence.

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References

    1. Kaplan MJ. Apoptosis in systemic lupus erythematosus. Clin Immunol. 2004;112:210–218. doi: 10.1016/j.clim.2004.04.007. - DOI - PubMed
    1. Schedel J, Gay RE, Kuenzler P, Seemayer C, Simmen B, Michel BA, Gay S. FLICE-inhibitory protein expression in synovial fibroblasts and at sites of cartilage and bone erosion in rheumatoid arthritis. Arthritis Rheum. 2002;46:1512–1518. doi: 10.1002/art.10309. - DOI - PubMed
    1. Liu H, Pope RM. The role of apoptosis in rheumatoid arthritis. Curr Opin Pharmacol. 2003;3:317–322. doi: 10.1016/S1471-4892(03)00037-7. - DOI - PubMed
    1. Richez C, Blanco P, Rifkin I, Moreau JF, Schaeverbeke T. Role for toll-like receptors in autoimmune disease: The example of systemic lupus erythematosus. Joint Bone Spine. 2011;78:124–130. doi: 10.1016/j.jbspin.2010.09.005. - DOI - PubMed
    1. Okayama N, Fujimura K, Suehiro Y, Hamanaka Y, Fujiwara M, Matsubara T, Maekawa T, Hazama S, Oka M, Nohara H, Kayano K, Okita K, Hinoda Y. Simple genotype analysis of the Asp299Gly polymorphism of the Toll-like receptor-4 gene that is associated with lipopolysaccharide hyporesponsiveness. J Clin Lab Anal. 2002;16(1):56–58. doi: 10.1002/jcla.2075. - DOI - PMC - PubMed

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