Format

Send to

Choose Destination
BMC Immunol. 2015 Feb 12;16:7. doi: 10.1186/s12865-015-0070-7.

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

Author information

1
Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institute, SE-171 76, Stockholm, Sweden. agneta.zickert@karolinska.se.
2
Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institute, SE-171 76, Stockholm, Sweden. pamoudru@its.jnj.com.
3
Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institute, SE-171 76, Stockholm, Sweden. yvonne.sundstrom@ki.se.
4
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. johan.ronnelid@igp.uu.se.
5
Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institute, SE-171 76, Stockholm, Sweden. vivianne.malmstrom@ki.se.
6
Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institute, SE-171 76, Stockholm, Sweden. iva.gunnarsson@karolinska.se.

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.

PMID:
25887118
PMCID:
PMC4326189
DOI:
10.1186/s12865-015-0070-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center