IL-17 and IL-23 in lupus nephritis - association to histopathology and response to treatment

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. We studied various cytokines, including the IL-23/IL-17 axis, in association to histopathology and response to therapy. Fifty...

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Published in:BMC immunology 2015-02, Vol.16 (1), p.7-7, Article 7
Main Authors: Zickert, Agneta, Amoudruz, Petra, Sundström, Yvonne, Rönnelid, Johan, Malmström, Vivianne, Gunnarsson, Iva
Format: Article
Language:English
Subjects:
Adolescent
Adult
Biomarkers, Pharmacological - blood
Bone morphogenetic proteins
Disease Progression
Female
Genetic aspects
Health aspects
Humans
Immunohistochemistry
Immunosuppressive Agents - therapeutic use
Interleukin-17 - blood
Interleukin-23 - blood
Kidney - drug effects
Kidney - immunology
Lupus Nephritis - diagnosis
Lupus Nephritis - drug therapy
Lupus Nephritis - pathology
Male
Medical research
Medicine, Experimental
Middle Aged
Predictive Value of Tests
Prognosis
Th17 Cells - drug effects
Th17 Cells - immunology
Young Adult
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Gunnarsson, Iva
description 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. We studied various cytokines, including the IL-23/IL-17 axis, in association to histopathology and response to therapy. Fifty-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. At baseline, all patients had high disease activity (BILAG A/B). Baseline levels of IL-6, IL-10, IL-17, IL-23 (p 
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We studied various cytokines, including the IL-23/IL-17 axis, in association to histopathology and response to therapy. Fifty-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. At baseline, all patients had high disease activity (BILAG A/B). Baseline levels of IL-6, IL-10, IL-17, IL-23 (p &lt; 0.001) and IFN-γ (p = 0.03) were increased in patients vs. In contrast, TGF-β was lower in patients compared to controls (p &lt; 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 &lt; 0.03). At follow-up, IL-23 were higher in BILAG-non-responders vs. responders (p &lt; 0.05). Immunostaining of renal tissue revealed IL-17 expression in inflammatory infiltrates. 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We studied various cytokines, including the IL-23/IL-17 axis, in association to histopathology and response to therapy. Fifty-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. At baseline, all patients had high disease activity (BILAG A/B). Baseline levels of IL-6, IL-10, IL-17, IL-23 (p &lt; 0.001) and IFN-γ (p = 0.03) were increased in patients vs. In contrast, TGF-β was lower in patients compared to controls (p &lt; 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 &lt; 0.03). At follow-up, IL-23 were higher in BILAG-non-responders vs. responders (p &lt; 0.05). Immunostaining of renal tissue revealed IL-17 expression in inflammatory infiltrates. High 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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>25887118</pmid><doi>10.1186/s12865-015-0070-7</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Biomarkers, Pharmacological - blood
Bone morphogenetic proteins
Disease Progression
Female
Genetic aspects
Health aspects
Humans
Immunohistochemistry
Immunosuppressive Agents - therapeutic use
Interleukin-17 - blood
Interleukin-23 - blood
Kidney - drug effects
Kidney - immunology
Lupus Nephritis - diagnosis
Lupus Nephritis - drug therapy
Lupus Nephritis - pathology
Male
Medical research
Medicine, Experimental
Middle Aged
Predictive Value of Tests
Prognosis
Th17 Cells - drug effects
Th17 Cells - immunology
Young Adult
title IL-17 and IL-23 in lupus nephritis - association to histopathology and response to treatment
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