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

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

Zickert, Agneta (author): Karolinska Institutet

Amoudruz, Petra (author)

Sundstrom, Yvonne (author): Karolinska Institutet

Rönnelid, Johan (author): Uppsala universitet,Klinisk immunologi

Malmstrom, Vivianne (author): Karolinska Institutet

Gunnarsson, Iva (author): Karolinska Institutet

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2015-02-12
2015
English.
In: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 16

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Journal article (peer-reviewed)

Abstract Subject headings

Background: 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. Methods: Fifty-two patients with active LN were included. Renal biopsies were performed at baseline and after immunosuppressive treatment. Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-10, IL-17, IL-23 and TGF-beta 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. Results: At 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-gamma (p = 0.03) were increased in patients vs. controls. In contrast, TGF-beta 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. Conclusions: 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)

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By the author/editor: Zickert, Agneta; Amoudruz, Petra; Sundstrom, Yvonn ...; Rönnelid, Johan; Malmstrom, Vivia ...; Gunnarsson, Iva

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

Articles in the publication: BMC Immunology

By the university: Uppsala University; Karolinska Institutet

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