JIA refers to a group of chronic childhood arthropathies of unknown aetiology. SLE is the prototypic systemic autoimmune disease and is characterized by B cell hyperreactivity and the production of autoantibodies [
1]. Chronic arthritis, a common feature of JIA and SLE, in the past was mainly attributed to dysregulated tolerance mechanisms of the adaptive immune system, particularly T-cells. However, the innate immune system has an important role in the pathogenesis of arthritis. Toll-
like receptors (TLRs) are a key link between infection, injury and inflammation [
2]. They recognize pathogen- and danger-associated molecular patterns (PAMPs and DAMPs), and subsequently trigger a pro-inflammatory cascade, which induces the transcription of multiple proinflammatory cytokine genes as well as dendritic cell maturation [
3,
4]. Cell wall components of various Gram-positive and Gram-negative pathogens, stress proteins and cell decomposition products are predominantly identified by the Toll-
like receptors 2 and 4 [
3,
5]. Although TLR-mediated inflammation is an important aspect of host defense, it is also linked to pathogenesis of several autoimmune diseases, like rheumatoid arthritis (RA) and SLE [
4,
6‐
9]. Feedback loops between DAMPS, PAMPs and their overlapping receptors may link infectious triggers and disease flares [
10]. Self-molecules, (e.g. S100 proteins) indicating synovial tissue damage amplify inflammatory arthritis [
11]. Serum concentrations of S100A8/S100A9 proteins correlate well with the disease activity in children [
12]. Some studies suggest that patients with clinically inactive JIA, but elevated levels of S100A proteins, may be at risk for disease flares [
13]. Children with systemic onset of JIA show up to 20-fold higher S100A serum protein concentrations than those found in other inflammatory disorders. In SLE elevated serum concentrations also correlate significantly with disease activity index [
14]. The elevated expression levels of Toll-
like receptors 2, TLR3 and TLR4 have already been associated with the chronic joint inflammation in adult RA patients [
15,
16].
Associations between different polymorphisms within the TLR2 and TLR4 genes or within the promoter region of the TLR9 gene and susceptibility for RA and SLE are subjects of great controversy [
17‐
19]. Few studies exist to date on the importance of innate immunity and of, in particular, Toll-
like receptors in the pathogenesis of JIA and SLE. Recently, two common cosegregating missense mutations, Asp299Gly and Thr399Ile, affecting the extracellular domain of the TLR4 protein, have been characterized [
20]. Both mutations lead to an attenuated efficacy of lipopolysaccharide signaling and a reduced capacity to elicit inflammation. Also for the TLR2 gene two SNPs (Arg677Trp and Arg753Gln) have been identified that abrogate the ability of TLR2 to mediate a response to bacterial cell wall components [
21].
DAMPS are found in high concentrations in inflamed tissue, where neutrophils and monocytes belong to the most abundant cell types. We hypothesized that the enduring local inflammation triggered by DAMPS may correlate with levels of TLR protein expression on CD14+ monocytes. We therefore decided to investigate the TLR2 and TLR4 protein expression on CD14+ monocytes of JIA and pediatric SLE patients during active and inactive disease phases as well as the TLR expression levels of healthy individuals. Furthermore we hypothesized that the two single nucleotide polymorphisms (SNPs) of TLR2-gene (Arg677Trp and Arg753Gln) and TLR4-gene (Asp299Gly and Thr399Ile) are implicated in the pathogenesis of JIA and SLE. The current study compared the allele frequency and genotype distribution for these mutations among JIA respectively SLE patients and healthy control subjects.