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AB0177 Toll-Like Receptors - Differences between Healthy Control, ANCA Associated Vasculitis and Lupus Kindeys - Preliminary Pilot Study
  1. H. Ciferska1,
  2. V. Tesar2,
  3. E. Honsova3,
  4. A. Lodererova3,
  5. Z. Hruskova2,
  6. K. Pavelka1
  1. 1Rheumatology Institute, Rheumatology Institute
  2. 2Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General University Hospital
  3. 3Pathology Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Abstract

Background Systemic lupus erythematosus (SLE) is characterized by a defective monocyte/macrophage-mediated clearance of the apoptotic (nucleic acid-containing) particles in vitro. The large amount of nucleic acids, free and/or complexed, are present in circulation and/or locally released. They can be entrapped in kidney from the blood stream.On the other hand bacterial infections are associated with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Our hypothesis is that those nucleic acids are bound by renal Toll-like receptors (TLR). TLRs participate in innate immune response through their ability to recognize and bind to various microbial structures. This might lead to cross-reactions with endogenous nucleic acids, which can escape clearence of apoptotic rests, leading to renal injury.

Objectives Our objective was to assess and compare expresion of TLR-7,-8 and -9 in healthy controls, ANCA associated vascuitis and lupus kidneys.

Methods The residual paraffin embedded kidney biopsy samples were used for this study. There were 8 samples with lupus nephritis (LN) (6 females and 2 males) (class II 2 patients, class III 6 patients), 5 samples with AVV with renal involvement and 3 controls without glomerular disease (wedge biopsies obtained during transplantation surgery). The following antibodies were used for the immunohistochemistry: anti-TLR-7 (LSBio,Seattle, WA) and anti -TLR-8 and -9 (Sigma-Aldrich,St.Louis, MO).

Results Normal kidney contained some single-stranded RNA binding (TLR-8) receptors but in particular double-stranded RNA binding receptor TLR-7 mostly in distal tubuli and minimal expersion of DNA binding TLR-9 was found. SLE kidneys contained more TLR-7, TLR-8 and TLR-9 then healthy controls, however the stronger expression of TLR-8 and -9 was found in tubuli of patients with AAV.

Conclusions It is concluded that kidneys have a capacity to bind nucleic acids and that this ability is altered in different types of glomerulonephritides in SLE and AAV. TLR stimulation leads to the production of tumor necrosis factor-α and of other pro-inflammatory cytokines and to up-regulation of co-stimulatory molecules necessary for the adaptive immune response, which is possibly directed against endogenous nucleic acids.

Acknowledgements Supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00023728 (Institute of Rheumatology)

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.3235

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