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

BMC Immunol. 2015 Feb 12;16(1):7. doi: 10.1186/s12865-015-0070-7.

Abstract

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-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.

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-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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Pharmacological / blood*
  • Disease Progression
  • Female
  • 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
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Young Adult

Substances

  • Biomarkers, Pharmacological
  • Immunosuppressive Agents
  • Interleukin-17
  • Interleukin-23