Clinical significance of TLR3 and TLR4 in peripheral blood mononuclear cells from children with Henoch-Schönlein purpura nephritis

Abstract

The aim of the present study was to investigate the expression levels and clinical significance of Toll-like receptor (TLR) 3 and 4 in peripheral blood mononuclear cells (PBMCs) collected from children with Henoch-Schönlein purpura (HSP) nephritis. The randomized controlled trial was conducted between August 2011 and March 2013, and 105 children with a clinical diagnosis of HSP were enrolled in the study. According to the 24-h urinary protein measurements and the presence of renal damage, the 105 cases were divided into groups A, B and C as follows: Group A, children with HSP but without renal damage; group B, children with HSP nephritis but without proteinuria; group C, children with HSP nephritis and proteinuria. A total of 30 healthy children were enrolled in the normal control group (group N). The primary endpoints were the detection of TLR3 and 4 mRNA and protein expression levels in PBMCs by flow cytometry and quantitative polymerase chain reaction. The mRNA and protein expression levels of TLR4 in the PBMCs were significantly higher in groups A, B and C when compared with group N. In addition, the mRNA and protein expression levels of TLR4 in group C were much higher when compared with groups A and B. A positive correlation was identified between TLR4 protein expression and 24-h urinary protein levels in group C. The expression levels of TLR3 did not significantly differ among the groups. Protein and mRNA expression levels of TLR4 in PBMCs significantly increased and exhibited a positive correlation with urinary protein excretion. These results indicate that aberrant activation of TLR4 may be relevant to the development of HSP nephritis.

Different Expression Patterns of Toll-Like Receptor mRNAs in Blood Mononuclear Cells of IgA Nephropathy and IgA Vasculitis with Nephritis

“…Currently, information regarding signaling of TLRs in glomerular diseases is limited (Mao and Huang 2014). Tables 6 and 7 summarize previously reported data and our data of expression of TLR mRNAs in PBMCs from IgAN (Coppo et al 2009;Donadio et al 2014;Li et al 2014) and from IgAV patients with or without renal involvement (Chang et al 2014;Donadio et al 2014). There are several differences in the backgrounds of enrolled patients among the previous studies and our study.…”

“…Suzuki et al (2008) investigated expression levels of TLR2, TLR4, and TLR9 mRNAs in splenocytes from ddY mice, which develop IgAN spontaneously, and showed activation of the TLR9 pathway. Up-regulation of TLR4 was found in PBMCs from patients with IgAN by Coppo et al (2009), children with IgAN and IgAV by Donadio et al (2014), and children with IgAV by Chang et al (2014). Li et al (2014) reported up-regulation of TLR9 in PBMCs from IgAN patients.…”

“…Abnormal expression levels of TLRs were shown in an animal model of IgAN (Suzuki et al 2008) and in patients with IgAN and IgAV (Coppo et al 2009;Chang et al 2014;Donadio et al 2014;Li et al 2014). These studies investigated expression levels of TLRs in splenocytes or peripheral blood mononuclear cells (PBMCs) by real-time reverse transcription polymerase chain reaction (RT-PCR) and/or flow cytometry.…”

The epipharynx-kidney axis triggers glomerular vasculitis in immunoglobulin A nephropathy

“…Upregulation of TLRs has been observed in upper respiratory tract infections [35]. Additionally, abnormal expression levels of TLRs were demonstrated in an animal model of IgAN and in patients with IgAN and IgA vasculitis [36][37][38][39][40][41]. It is conceivable that chronic inflammation of the epipharynx, which is extremely common in patients with IgAN, is the underlying condition responsible for the upregulation of TLRs in a considerable percentage of patients with IgAN.…”

Cell Membrane-bound TLR2 and TLR4: Potential Predictors of Active Systemic Lupus Erythematosus and Lupus Nephritis

“…There is an increasing body of evidence that activation of mbTLR also underlies other types of immune-mediated nephritis in humans. As an example, a study showed an enhancement of TLR4 in mononuclear cells from children with Henoch-Schönlein purpura and high-grade proteinuria 11 .…”