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 . 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.
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
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