The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases

ten Oever, Jaap; Kox, Matthijs; van de Veerdonk, Frank L; Mothapo, Khutso M; Slavcovici, Adriana; Jansen, Tim L; Tweehuysen, Lieke; Giamarellos-Bourboulis, Evangelos J; Schneeberger, Peter M; Wever, Peter C; Stoffels, Monique; Simon, Anna; van der Meer, Jos WM; Johnson, Melissa D; Kullberg, Bart-Jan; Pickkers, Peter; Pachot, Alexandre; Joosten, Leo AB; Netea, Mihai G

An important aspect of this study is the possibility to use soluble TLRs as diagnostic markers. Rapid and reliable differentiation of non-infectious inflammatory disorders from infections, and the classification of infections according to their microbiological etiology is essential for optimal treatment of these conditions. So far, only a small number of studies have been published on sTLRs as diagnostic biomarkers. A few studies from the same group reported that intrauterine infections in pregnant women are characterized by elevated levels of sTLR1, sTLR2, sTLR6 and sTLR4 in the amniotic fluid [9, 10, 13] , supporting the concept of sTLR release during infections. We assessed the value of sTLR2 and sTLR4 levels to discriminate between several inflammatory conditions. sTLR2 and sTLR4 were elevated in response to inflammatory insults and particularly sTLR4 showed a good specificity to discriminate between an infection and a non-infectious inflammatory conditions such as gout, Crohn's disease, rheumatoid arthritis or autoinflammatory syndromes. Moreover, sTLR4 concentrations show a high specificity for discriminating between bacterial and viral infections using high cut-off values, but sensitivity was low. We have to mention however that the overall discriminative value of sTLR levels was not superior to that of CRP in the relatively small group of patients assessed in this study Future larger validation studies should demonstrate the overall value of sTLR2 and sTLR4 levels for the diagnosis of infections and autoinflammatory diseases in relation to that of classic inflammatory markers. Furthermore, besides sTLRs, other soluble pattern recognition receptors such as the soluble mannose receptor that are shed during cell stimulation with β-glucans are also interesting candidates for new and potentially more specific diagnostic biomarkers [31] .