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THU0520 Interferon (IFN)-Lambda1/3, but not IFN-Alpha, is A Marker of Poor Response to Treatment in Lupus Nephritis
  1. A. Zickert,
  2. V. Oke,
  3. I. Parodis,
  4. E. Svenungsson,
  5. I. Gunnarsson
  1. Department of medicine, Unit of rheumatolgy, Karolinska Institute, Stockholm, Sweden

Abstract

Background Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) affecting up to 60% of the patients. IFN-α is a central cytokine in the pathogenesis for LN, and recent studies also indicate a role for IFN-λ1/3. However little is known about these cytokines in the context of treatment response and how they are affected by immunosuppressive therapy in LN.

Objectives We studied serum levels of IFN-α and IFN-λ1/3 in patients with LN, both at active disease and after induction treatment. Associations with clinical and histological response to treatment were evaluated.

Methods Fifty-six patients with active LN, 45 proliferative- (PN) and 11 membranous nephritis (MN), were included. Renal biopsies were performed at baseline and after induction immunosuppressive treatment (median 7 months). Clinical and routine laboratory data were collected, and serum levels of IFN-α and IFN-λ1/3 were analysed by ELISA at both biopsy occasions and in 163 healthy controls. The cut-off for IFN-α was 0.02 pg/l and for IFN-λ1/3 0.3 pg/l. Biopsies were evaluated according to the ISN/RPS classification and scored for activity and chronicity indices. Clinical response was defined according to recent definitions [1]. Histological response (HR) was defined as Class I, II or III/IV-C on repeat biopsies.

Results At baseline, serum levels of both IFN-α and IFN-λ1/3 were higher in patients vs. controls (p=0.01 and 0.03 respectively). There was no correlation between IFN-α and IFN-λ1/3. There was a trend towards higher levels of IFN-α in patients with PN vs. MN (p=0.06) and higher IFN-λ1/3 in MN vs. PN (0.09). In PN, 73% of the patients had detectable IFN-α vs.36% in MN (p=0.02). In all patients, IFN-α decreased after treatment (p=0.002) but IFN-λ1/3 remained unchanged. However in patients with HR, levels of IFN-λ1/3 decreased (p=0.01). Of histological non-responders, 31% had detectable levels of IFN-λ1/3 at follow-up, vs 10% of HR (p=0.05). IFN-α was positively correlated to anti-DNA and anti-C1q-antibodies and negatively to C3 and C4, but no correlations were seen for IFN-λ1/3. Neither IFN-α, nor IFN-λ1/3 correlated to proteinuria or creatinine and there was no clear association to clinical response.

Conclusions Our results support a role for IFN-λ1/3, and also confirms previous findings of involvement of IFN-α, in LN. Interestingly, IFN-α and INF-λ1/3 did not correlate to each other and their levels were affected differently by immunosupressive treatment, and also differed between MN and PN. Persistently elevated levels of IFN-λ1/3 indicated poor histological response to treatment. The study indicates that IFN-α and IFN-λ1/3 may be differently involved in subgroups of LN and that IFN-λ1/3 may be a potential biomarker for treatment response.

References

  1. Gordon C, Jayne D, Pusey C, et al. European consensus statement on the terminology used in the management of lupus glomerulonephritis. Lupus 2009;18(3):257-63

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.5505

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