title: 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.
  
  
  METHODS
  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.affiliation: Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institute, SE-171 76, Stockholm, Sweden. agneta.zickert@karolinska.se.
authors.forename: Agneta
authors.initials: A
authors.lastname: Zickert
authors.affiliation: Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institute, SE-171 76, Stockholm, Sweden. pamoudru@its.jnj.com.
authors.forename: Petra
authors.initials: P
authors.lastname: Amoudruz
authors.affiliation: Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institute, SE-171 76, Stockholm, Sweden. yvonne.sundstrom@ki.se.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Sundström
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. johan.ronnelid@igp.uu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
authors.affiliation: Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institute, SE-171 76, Stockholm, Sweden. vivianne.malmstrom@ki.se.
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
authors.affiliation: Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Karolinska Institute, SE-171 76, Stockholm, Sweden. iva.gunnarsson@karolinska.se.
authors.forename: Iva
authors.initials: I
authors.lastname: Gunnarsson
mesh_terms: D000293:Adolescent; D000328:Adult; D054316:Biomarkers, Pharmacological / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D020381:Interleukin-17 / Q000097:blood*; D053759:Interleukin-23 / Q000097:blood*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology; D008181:Lupus Nephritis / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D055815:Young Adult
chemical_list: D054316:Biomarkers, Pharmacological; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D053759:Interleukin-23