Background The role of Toll Like Receptors (TLRs) in Systemic Lupus Erythematosus (SLE) pathogenesis has raised great interest as they recognize nucleic acids, main antigens of the disease. Several studies on murine lupus support the role of TLRs in the onset and progression of glomerulonephritis. Data on kidney TLRs expression in humans are scarce; pattern of distribution within the kidney is controversial and TLRs expression has not yet been quantified.
Objectives Aim of the study was to locate and quantify TLR3, TLR7 and TLR9 in kidney sections of SLE patients and correlate TLRs expression with clinical and histological features of lupus nephritis (LN).
Methods Biopsy samples from SLE patients admitted to the Lupus Clinic, Sapienza Università di Roma, were evaluated. As control, kidney from 4 patients undergoing nephrectomy for malignancies was analysed. LN was classified according to the 2003 ISN/RPN Classification. The specimens were analysed by immunohistochemistry using anti-human TLR3/7/9 MoAb; in addition, the number of positive nuclei/mm2 was quantified by a dedicated software. LN activity index (AI) and chronicity index (CI) were assessed according to the NIH scoring system. Data were expressed as mean±standard deviation or median (range) when non parametric; Mann-Whitney and Spearman tests were used. A p value ≤0.05 was considered statistically significant.
Results Table 1 shows demographic and clinical data of the 26 patients evaluated.
Kidney biopsies were classified as class II (n=6), class III (n=9), class IV (n=9), class V (n=1) and class VI (n=1). In the LN specimens all the TLRs evaluated showed a diffuse expression without a significant difference between glomerular and tubular staining. Compared to controls, LN showed a significantly higher amount of whole kidney TLR3 (p=0.023) and TLR9 (p=0.024) and tubular TLR7 (p=0.018). When comparing TLRs expression in different histological classes, we detected a significantly higher glomerular expression of TLR3 in class III vs class II (p=0.033) and both tubular and glomerular TLR9 in class IV vs classes II and III (p=0.021, p=0.043 and p=0.050, p=0.012, respectively). In class IV, TLR7 showed a more intense staining over the others, especially in the glomerulus. We found a positive correlation between glomerular TLR9 and AI (r=0.6, p=0.0063) and between tubular TLR7 and CI (r=0.6, p=0.026). Moreover, we found a positive correlation between tubular TLR9 and renal-SLEDAI (r=0.54, p=0.01).
Conclusions The findings of this study confirm that TLRs are diffusely over-expressed in kidney sections from LN patients by quantifying their glomerular and tubulointerstitial expression compared to control biopsies. Proliferative LN showed a higher expression of glomerular TLR3 and TLR9. The latter was the only one positively associated to AI. Interstitial infiltrates are more commonly detected in proliferative LN and represent a poor prognostic factor. Class IV LN, the one associated to a worse outcome, also showed tubulointerstitial expression of both TLR7 and TLR9.
Disclosure of Interest None declared
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