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

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.

• Authors: Agneta Zickert, Petra Amoudruz, Yvonne Sundström, Johan Rönnelid, Vivianne Malmström, Iva Gunnarsson
• Journal: BMC immunology (BMC Immunol) Vol. 16 Pg. 7 (Feb 12 2015) ISSN: 1471-2172 [Electronic] England
• PMID: 25887118 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adolescent
• Adult
• Biomarkers, Pharmacological (blood)
• Disease Progression
• Female
• Humans
• Immunohistochemistry
• Immunosuppressive Agents (therapeutic use)
• Interleukin-17 (blood)
• Interleukin-23 (blood)
• Kidney (drug effects, immunology)
• Lupus Nephritis (diagnosis, drug therapy, pathology)
• Male
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Th17 Cells (drug effects, immunology)
• Young Adult