Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Serum Cytokines in Lupus Nephritis, Levels of IL-17 and IL-23 in Association to Histopathology and Response to Treatment.

Zickert1,  Agneta, Amoudruz1,  Petra, Ronnelid2,  Johan, Malmstrom1,  Vivianne, Gunnarsson1,  Iva

Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden
Uppsala University, Uppsala, Sweden

Background/Purpose:

The pathogenesis for lupus nephritis (LN) is complex and involves many components of the immune system. Recent studies indicate an important role for the T-cell subset Th-17, and the associated cytokines IL-17 and IL-23, in LN. Increased knowledge of cytokines in LN, originating from both the innate and adaptive immune system, may contribute to further understanding of the pathogenesis, identification of new biomarkers and to development of new treatment strategies.

The aim of the study was to investigate cytokines, previously indicated in LN, in association to clinical and histopathological findings and response to therapy.

Methods:

Fifty-two patients with active lupus nephritis were included. Renal biopsies were performed at baseline and after 6 months of standard induction treatment. Clinical and laboratory data were collected at baseline and at repeated biopsies and serum levels of TNFa, IFNg, IL-2, IL-4, IL-6, IL-10, IL-6R, IL-17, IL-21, IL-23 and TGF-b were analyzed at both occasions. Biopsies were evaluated regarding WHO-classification and renal disease activity was estimated using the BILAG index. An improvement of at least 2 grades in renal BILAG was regarded complete response (CR), whereas 1 grade as partial response (PR). Serum samples from 13 healthy volunteers were used as controls.

Results:

Baseline biopsies showed WHO-class III-IV (n=44) and V (n=8) and all patients had high renal disease activity (BILAG A/B). Follow-up biopsies showed WHO I-II (n= 19), III-IV (n=19) or V (n= 14). 22 patients were regarded CR, 20 PR and 10 non responders. At baseline, serum levels of IL-6, IL-10, IFNg, IL-17-1L-23 and IL-6R were significantly higher in patients vs. controls and TGFb was significantly lower (p<0.05 for all). Overall, the high cytokine levels except IFN g decreased significantly after treatment.

Serum levels of IL-17 at baseline were significantly higher in patients with a persisting active nephritis at follow up (WHO III, IV or V) vs. those with a good histopathological response (WHO I or II) (p<0.01). The highest levels of IL-17 were found in class V. Overall, BILAG non-responders had significantly higher levels of IL-23 at follow up vs. CR and PR (P<0.05), most pronounced among non-responder patients with WHO class V at follow up (p<0.02).

Conclusion:

Levels of IL-17 at baseline were significantly higher in patients not responding histopathologically to treatment, suggesting that patients with high levels of IL-17 may represent a subgroup of patients with more severe disease. Levels of IL-23 at follow up were significantly higher in BILAG non-responders than in responders, especially in LN class V. This study indicates a role for Th-17 (IL-17/IL-23) in LN regarding treatment response, especially in class V LN, and suggests that these cytokines may be used as biomarkers.

To cite this abstract, please use the following information:
Zickert, Agneta, Amoudruz, Petra, Ronnelid, Johan, Malmstrom, Vivianne, Gunnarsson, Iva; Serum Cytokines in Lupus Nephritis, Levels of IL-17 and IL-23 in Association to Histopathology and Response to Treatment. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1658
DOI:

Abstract Supplement

Meeting Menu

2011 ACR/ARHP