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

We 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.