Background Toll-like receptors (TLRs) are trans-membrane receptors expressed on immune and non-immune cells that recognize pathogen-associated molecular patterns (PAMPs) and self-molecules termed as damage-associated molecular patterns (DAMPs).
Objectives To investigate the expression Toll-like receptors (TLRs) 4 and 9 in the peripheral blood of patients with systemic lupus erythematosus (SLE) and Dermatomyositis (DM) as well as muscle tissue specimens from the DM patients to explore their role and study their correlations with clinical manifestations and disease activity of both diseases.
Methods Disease activitiy was defined by SLE Disease Activity Index (SLEDAI) score and DM disease activity score (DAS). SLE-related organ damage was assessed by the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index. Buffy coats and deltoid muscle specimens were immediately frozen and stored at -80°C till further processing of TLR4 and TLR9 gene expression analysis by the quantitative PCR technique.
Results SLE patients had significantly higher TLR4 and TLR9 expression in the peripheral blood than the control (93.77±74.64 and 87.9±74.9 relative units) (46.01±11.30 and 5.7±3.7 relative units) (p<0.05 and p<0.001) respectively. TLR4 expression levels in the peripheral blood were statistically significantly higher p<0.05 in SLE patients who had malar rash, alopecia,arthritis and pericarditis, while TLR9 expression levels were positively correlated with the protien/creatinine ratios (p<0.05), anti ds-DNA titers (p<0.05), the SLICC damage indices (p<0.001) and negatively correlated with C3 levels (p<0.05).TLR4 and TLR9 expression levels were significantly higher (p<0.001) in the muscle tissue but not in the peripheral blood (52.4±11.7 and 8.3±2.3 relative units)than the control (6.9±2.3 and 0.6±0.5 relative units) respectively.Both TLR4 and TLR 9 expression levels in the muscle tissue from DM patients were significantly positively correlated with DAS scores (p<0.001) moreover TLR9 expression levels were significantly higher in patients who had calcinosis (p<0.05) and showed significant positive correlation with creatine kinase levels (p<0.05).
Conclusions Our results suggest a detrimental role of TLR signaling and innate immune system in the pathogenesis of SLE and DM through activation of TLR pathway and propose that targeting TLRs and their signaling pathways may lead to development of a new class of efficacious drugs for down-streaming the auto-inflammatory response and control disease activity in both SLE and DM disorders.
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Acknowledgements Thanks a lot for Prof.DR. Samia M Abdel Moneim for her great support and effort in reviewing this manuscript
Disclosure of Interest None declared
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