Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?
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.
KeywordsToll-like receptors Renal biopsy Renal insufficiency IgA nephropathy ANCA-associated vasculitis
Study was supported by a project of the Ministry of Health of the Czech Republic for conceptual research development by organization 023728 and by Grants LH15168, PROGRES Q25/LF1 and DRO VFN 64165 from the Ministry of Health of the Czech Republic. MS acknowledges the assistance provided by the Research Infrastructure NanoEnviCz supported by the Ministry of Education, Youth and Sports of the Czech Republic under Project No. LM2015073. JN was supported in part by Grants DK078244 and DK082753 from the National Institutes of Health.
HC, DM, ZH, JV and VT conceived and planned the experiments and worked on the manuscript. HC and AL carried out the experiments. EH and MS processed the experimental data, performed the analysis and the evaluation of the results. TZ, MN, RC and JN aided in interpreting the results and drafter and edited the manuscript. All authors discussed the results and commented on the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethical committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants involved in the study.
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