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Abstract: TH-PO1034

The Role of Expression of Toll-Like Receptors 4 and 9 in Stratification of Severity of IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Ciferska, Hana, Institute of Rheumatology, Praha, Czechia
  • Honsova, Eva, IKEM, Prague, Czechia
  • Hruskova, Zdenka, Department of Nephrology,General University Hospital and First Faculty of Medicine, Charles University, Prague 2, Czechia
  • Neprasova, Michaela, General Teaching Hospital in Prague, Dobris, Czechia
  • Suchanek, Miloslav, University of Chemical Technology Prague, Prague, Czechia
  • Zima, Tomas, Firts Faculty of Medicine, Charles University, Prague 2, Czechia
  • Coppo, Rosanna, Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy
  • Tesar, Vladimir, General University Hospital in Prague, Prague, Prague, Czechia
  • Novak, Jan, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Maixnerova, Dita, Dept. of Nephrology, Prague, Prague, Czechia
Background

The onset of IgA nephropathy (IgAN), characterized by glomerular deposition of IgA 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 specimens from cadavers and a disease controls (ANCA vasculitis).

Methods

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 (n=34) from controls. Moreover, patient with IgAN represented four subgroups based on eGFR and proteinuria. All biopsies of patients with IgAN were scored according to the Oxford Classification.

Results

LDA showed that TLR 4, 7, 8, and 9 staining was more intense in specimens from IgAN patients than in normal kidney tissues. LDA also distinguished four subgroups of patients with IgAN based on MEST scoring . The intensity of intrarenal staining of TLRs discriminated four groups of IgAN divided according severity of renal impairment and proteinuria.

Conclusion

Intrarenal staining of TLRs together with clinical parameters (serum creatinine, eGFR, and proteinuria) analyzed by LDA may be helpful in assessment of disease prognosis.
References: Supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00023728 (Institute of Rheumatology) and by PROGRES Q25/LF1. JN was supported in part by grants DK078244 and DK082753 from the National Institutes of Health.

Funding

  • Other NIH Support