Glomerular expression of toll-like receptor-9 in lupus nephritis but not in normal kidneys: implications for the amplification of the inflammatory response.
Toll-like receptors recognising self-derived nucleic acids may participate in the pathogenesis of autoimmune diseases. Following the description of an enhanced population of toll-like receptor-9 (TLR-9) expressing auto-antibody producing B lymphocytes in active lupus, we explored the expression of TLR-9 in the renal tissue of patients with lupus. TLR-9 expression was studied in the kidneys of 12 lupus and 10 control samples from macroscopically unaffected areas of patients with renal adenocarcinoma by immunohistochemistry. A semiquantitative score was assigned separately for tubular, interstitial and glomerular expression. TLR-9 was expressed in the renal tubules and interstitial tissue in both patients with lupus and controls. Six of 12 patients with lupus with proliferative or membranous nephritis - as compared to none of the controls - exhibited both tubulointerstitial and glomerular TLR-9 expression. Biopsies with glomerular TLR-9 expression had a higher activity index (mean +/- SD, 6.3 +/- 3.5 in the presence of TLR-9 glomerular expression as compared to 1.3 +/- 1.8 in its absence, P = 0.015, t-test). This study documents for the first time the up-regulation of TLR-9 within the glomerulus of patients with lupus nephritis. Activation of TLR-9 expressing glomerular cells by endogenous nucleic acids (nucleosomes) may amplify the inflammatory response.
Papadimitraki
E D
ED
Laboratory of Autoimmunity and Inflammation, Rheumatology, Clinical Immunology and Allergy, Medical School, University of Crete, Voutes, Heraklion, Greece.
Tzardi
M
M
Bertsias
G
G
Sotsiou
E
E
Boumpas
Dimitrios T
DT
D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes / Q000378:metabolism; D012720:Severity of Illness Index; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D055815:Young Adult
D000888:Antibodies, Anti-Idiotypic; D009707:Nucleosomes; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004247:DNA