Abstract
BackgroundToll-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 methodsTLR4 (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.ResultsCD14*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.ConclusionThe CD14 (-159)*T allele seems to be associated with susceptibility to SLE and arthritis occurrence.
Highlights
Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are common complex diseases characterized by a chronic generalized inflammation that may involve several tissues and organs
systemic lupus erythematosus (SLE) patients carrying CD14*T/T/Toll-like receptor 4 (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
In SLE patients analysis of TLR4 SNP along with clinical and biological features of SLE showed no significant correlations between this polymorphism frequencies and clinical manifestations, or with increased disease activity (SLEDAI > 8), or with an elevated titer of anti-nuclear antibodies (ANA), the presence of anti-dsDNA antibodies (Abs) and decreased complement activity (DCA)
Summary
Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are common complex diseases characterized by a chronic generalized inflammation that may involve several tissues and organs. FLIP (Fas-associated death domain Like Interleukin-1 converting enzyme Inhibitory Protein) [2,3] These immortal FLSs invade synovia and cartilage and load out metalloproteases leading to their destruction and release of extracellular matrix debris (EMD). 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. TLR4 (Asp299Gly) and CD14 (C/T −159) polymorphisms (SNPs) may modify qualitatively and/or quantitatively their expression They could be implied in autoimmune diseases and can influence both susceptibility and severity of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
