Surface expression and genotypes of Toll-like receptors 2 and 4 in patients with juvenile idiopathic arthritis and systemic lupus erythematosus

Abstract

Doc number: 9

Abstract

Background: Chronic arthritis is a common feature of juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE). It was subsequently discovered that Toll-like receptors (TLRs) are able to upregulate cytokine production in response to endogenous ligands released after tissue damage, suggesting that TLRs can maintain an inflammatory response even in absence of pathogen. Thus, TLRs may contribute to increased inflammation in JIA and SLE patients. The aim of this study was to investigate the role of TLRs in JIA and SLE. We examined the in vivo expression and polymorphisms of TLR2 and TLR4 in peripheral monocytes of patients with JIA and SLE during active and inactive disease phases.

Methods: This single center cohort study consisted of JIA and SLE affected children and control subjects. TLR2 and TLR4 protein expression on CD14⁺ monocytes was examined by flow cytometry. TLR2 and TLR4 genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism method (RFLP-PCR).

Results: A significant reduction in the level of TLR4 expression (p ≤ 0.001) was observed on monocytes of patients with JIA and SLE compared with that of healthy control subjects. There was no correlation between the TLR2 or TLR4 genotypes and the observed differential TLR protein expression on monocytes.

Conclusions: To conclude, our observations suggest involvement of investigated TLRs in the pathogenesis of JIA and SLE. It still remains to be elucidated whether reduced TLR4 expression is cause of chronic arthritis or a result of some feedback loop.