The onset of IgA nephropathy (IgAN), characterized by glomerular deposition of IgA-containing immune complexes, is often associated with synpharyngitic hematuria. Innate immune responses mediated by Toll-like receptors (TLR) may play a role in IgAN onset and/or progression. Here, we assessed the expression of TLR 4, 7, 8, and 9 in renal-biopsy specimens from patients with IgAN, with different degree of proteinuria and eGFR, compared with normal-kidney and disease-control tissues (ANCA-associated vasculitis). Renal-biopsy specimens from 34 patients with IgAN and 7 patients with ANCA-associated vasculitis were used. In addition, we used 15 healthy portions of renal-tissue specimens from kidneys after nephrectomy for cancer as control specimens. Expression of TLR 4, 7, 8, and 9 was assessed using immunohistochemical staining of paraffin-embedded renal-biopsy tissue specimens with specific antibodies and evaluated semiquantitatively by light microscopy. Linear discriminant analysis (LDA) was used to test whether intrarenal staining of TLR 4, 7, 8, and 9 distinguished patients with IgAN from controls or correlated with eGFR and/or proteinuria. eGFR was calculated using the creatinine-based formula. Moreover, the biopsies from patients with IgAN were scored according to the Oxford Classification. LDA showed that staining for TLR 4, 7, 8, and 9 was more intense in specimens from IgAN patients compared to normal kidney tissues. The intensity of intrarenal staining of TLRs discriminated four groups of IgAN patients with different eGFR and proteinuria and MEST scoring.

Department of Microbiology University of Alabama at Birmingham Birmingham AL 35294 2170 USA

Department of Nephrology 1st Faculty of Medicine and General University Hospital Charles University U Nemocnice 2 128 08 Prague 2 Czech Republic

Department of Pathology Institute of Clinical and Experimental Medicine 140 21 Prague Czech Republic

Faculty of Environment Jan Evangelista Purkyne University in Usti nad Labem 400 96 Usti nad Labem Czech Republic

Fondazione Ricerca Molinette Regina Margherita Hospital 10134 Turin Italy

Institute of Clinical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine and General University Hospital Charles University 128 08 Prague Czech Republic

Institute of Rheumatology 1st Faculty of Medicine Charles University 128 50 Prague Czech Republic

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IgA nephropathy