Toll-like receptor 4 expression is increased in circulating mononuclear cells of patients with immunoglobulin A nephropathy

Abstract

SummaryWe investigated Toll-like receptors (TLR-3, -4 and -7) expression in circulating mononuclear cells of patients with immunoglobulin A nephropathy (IgAN), a disease with debated relationships with mucosal immunity. TLR-4 expression (detected by fluorescence activated cell sorter) and mRNA transcriptional levels (Taqman) were significantly higher in patients with IgAN than in healthy controls (P = 0·00200 and P = 0·0200). TLR-3 and TLR-7 were not modified significantly. In IgAN patients proteinuria was correlated significantly with TLR-4 expression (P = 0·0312). In a group of nephrotic syndromes, TLR-3, -4 and -7 expression was similar to healthy controls. A significant difference in TLR-4 expression and mRNA levels was found between very active IgAN patients (proteinuria > 1 g/1·73 m 2 /day in association with severe microscopic haematuria) and inactive patients (proteinuria < 0·5 g/1·73 m 2 /day, with absent or minimal haematuria). No correlation with levels of aberrantly glycosylated IgA1, age, renal biopsy features or therapy was found. This study shows for the first time an up-regulation of TLR-4 in circulating mononuclear cells of patients with IgAN, particularly in association with proteinuria and heavy microscopic haematuria.

Immunoglobulin A nephropathy: a pathophysiology view

“…The mechanisms of this unbalance are still unknown. There is evidence that TLRs are possible culprits, both in the increased production of abnormal IgA1, as well in the aberrant glycosylation [67][68][69]. TRL9 are hyperexpressed in plasmocytoid dendritic cells in tonsils of patients with IgAN [68].…”

Hla Typing in Epidermolysis Bullosa Patients: Relevancy to Gluten Sensitivity

“…IgAN is a glomerular disease characterized by prevalent mesangial IgA deposits, frequently is associated with macroscopic haematuria at level of mucosal infections [16,17]. Emerging hypothesis revealed that in IgAN suffering subjects mucosal immune system is dealing with continuous antigenic challenge which leads to the production of nephritogenic IgA, and common microbial or food antigens may play the role of eliciting agents [18]. In this light, previous publications have shown a beneficial effect of a gluten-free diet in these patients by reducing the levels of anti-gliadin IgA [8,19].…”

Association between toll-like receptor 6 expression and auxiliary T cells in the peripheral blood of pediatric patients with allergic purpura

“…TLRs may also upregulate the expression of co-stimulating molecules on the surface of antigen-presenting cells, leading to the production of a variety of cytokines and promoting the activation of Th cells, thereby priming the adaptive immune response (23)(24)(25). The excessive activation of TLRs may lead to the occurrence and development of a variety of autoimmune diseases (26,27 The results of this study suggest that TLR6 protein expression and MYD88 mRNA expression levels in the PBMCs of pediatric patients with HSP were significantly elevated compared with those in control subjects, and that the expression of TLR6 was significantly positively correlated with MYD88 mRNA expression (P<0.01). The observations suggest that TLR6 mediates the production of inflammatory cytokines and is involved in the pathogenesis of HSP, potentially via MYD88-dependent signal transduction pathways.…”