Abstract
BackgroundRecent studies indicate a central role for the IL-23/IL-17 axis in the pathogenesis of lupus nephritis (LN) but the importance in the context of treatment outcome is unknown. We studied various cytokines, including the IL-23/IL-17 axis, in association to histopathology and response to therapy.MethodsFifty-two patients with active LN were included. Renal biopsies were performed at baseline and after immunosuppressive treatment. Serum levels of TNF-α, IFN-γ, IL-6, IL-10, IL-17, IL-23 and TGF-β were analysed at both biopsy occasions and in 13 healthy controls. IL-17 expression in renal tissue was assessed by immunohistochemistry. Biopsies were evaluated regarding WHO-classification and renal disease activity was estimated using the BILAG-index. Improvement of 2 grades in renal BILAG was regarded complete response, and 1 grade partial response.ResultsAt baseline, all patients had high disease activity (BILAG A/B). Baseline levels of IL-6, IL-10, IL-17, IL-23 (p < 0.001) and IFN-γ (p = 0.03) were increased in patients vs. controls. In contrast, TGF-β was lower in patients compared to controls (p < 0.001).Baseline levels of IL-17 were higher in patients with persisting active nephritis (WHO III, IV, V) after treatment, i.e. a poor histological response, vs. WHO I-II (p < 0.03). At follow-up, IL-23 were higher in BILAG-non-responders vs. responders (p < 0.05). Immunostaining of renal tissue revealed IL-17 expression in inflammatory infiltrates.ConclusionsHigh baseline IL-17 predicted an unfavourable histopathological response, and BILAG-non-responders had high IL-23, indicating that that a subset of LN-patients has a Th-17 phenotype that may influence response to treatment and could be evaluated as a biomarker for poor therapeutic response.
Highlights
Recent studies indicate a central role for the IL-23/IL-17 axis in the pathogenesis of lupus nephritis (LN) but the importance in the context of treatment outcome is unknown
It is produced by other cells, such as T-cell receptor (TCR)γδ and TCRαβ double negative (DN) T-cells (CD3 + CD4-CD8-) [9]
Renal activity and histopathology All patients had an active nephritis at baseline with biopsies showing World Health Organization (WHO) class III (n = 15), III/V (n = 4), IV (n = 24), V (n = 8) and one glomerular vasculitis
Summary
Recent studies indicate a central role for the IL-23/IL-17 axis in the pathogenesis of lupus nephritis (LN) but the importance in the context of treatment outcome is unknown. The exact mechanisms remain unclear, the hallmark in the pathogenesis is production of autoantibodies and immune complex formation with subsequent infiltration by inflammatory cells in renal tissue [2,3,4]. IL-17 is the main cytokine from Th17 cells, a T-cell subset evolved from CD4+ Tcells under the influence of IL-6, IL-21 and IL-1. It is produced by other cells, such as T-cell receptor (TCR)γδ and TCRαβ double negative (DN) T-cells (CD3 + CD4-CD8-) [9]. Increased number of Th17 cells as well as high serum levels of IL-17 has been demonstrated in lupus patients
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