O’SULLIVAN, K.M1, FORD, S.L1, KITCHING, A.R.1,2 HOLDSWORTH, S.R.1,2
1Centre for Inflammatory Diseases, Dept. Of Medicine, Monash University, Clayton; Australia, 2Dept. of Nephrology, Monash Health Clayton, Australia
Aim: We sought evidence of aberrant renal TLR expression in 46 patients with acute crescentic glomerulonephritis (38 ANCA associated vasculitis, 8 Lupus Nephritis)
Background: Infections can initiate and exacerbate disease in patients with crescentic glomerulonephritis (GN) and provoke disease relapse. TLRs may be the possible link between infection and autoimmunity.
Methods: Multi colour confocal microscopy was used to examine kidney biopsies from patients with a first presentation of AAV (38), Lupus Nephritis (8) and controls (10) and stained for TLR2, TLR4 and TLR9, CD34, nephrin, CD68 (macrophages), and neutrophil elastase. The extent of staining was measured using Image J, and correlated with both clinical and histological parameters.
Results: TLR2, TLR4 and TLR9 expression was significantly increased in the AAV patient biopsies in both the glomeruli and tubulointerstitium, compared to controls (all, P<0.05).TLR2 expression was significantly increased within the glomeruli and tubulointerstitium of AAV patients compared to the LN patients (P<0.05), whereas there was no significant difference in TLR4 and TLR9 expression between the two disease groups. There was significant col-localisation of each TLR and its known ligand (High Mobility Group Box 1, and Fibrinogen), indicative of a functional relevance.TLR2 and TLR4 were predominantly expressed on endothelial cells, podocytes and leukocytes, whereas TLR9 was expressed by podocytes and infiltrating glomerular macrophages. TLR2 and TLR4 expression correlated inversely with presenting eGFR (P=<0.02).
Conclusions: TLR2, TLR4 and TLR9 expression in biopsies from AAV and LN patients is dysregulated. LN patients had enhanced renal TLR expression but not to the same extent as AAV patients. These results suggest that TLR expression is significantly increased in AAV compared to LN, indicating these receptors may be a potential target for therapeutics.