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Abstract
Objectives Interferon (IFN)-α is thought to be central in the pathogenesis for lupus nephritis (LN) and recent studies also indicate a role for IFNλ. Little is known about these cytokines in the context of treatment response. We studied levels of IFNα and IFNλ in patients with LN in association with clinical and histological response (HR) to treatment.
Methods Fifty-six patients with active LN were included. Renal biopsies were performed at baseline and after immunosuppressive therapy. Serum levels of IFNα and IFNλ were analysed at both biopsy occasions and in 163 controls. The biopsies were evaluated according to the International Society of Nephrology/Renal Pathology Society classification. Clinical response was defined according to recent definitions. HR was defined as class I, II or III/IV-C on repeat biopsies. The expression of IFNλ in renal tissue was assessed by immunohistochemistry.
Results At baseline, serum levels of both IFNα and IFNλ were higher in patients versus controls (p=0.01 and p=0.03, respectively). There was no correlation between IFNα and IFNλ. Overall, IFNα decreased after treatment (p=0.003) but IFNλ remained unchanged. However in patients with HR, IFNλ decreased (p=0.01). The highest levels of IFNλ were seen in patients with poor HR. Immunostaining of renal tissue revealed expression of IFNλ, particularly in crescent formations, inflammatory infiltrates and tubular cells.
Conclusions The study supports a role for IFNλ in LN, both in circulation and at a tissue level. Levels of IFNα and IFNλ did not correlate and were affected differently by immunosuppression, indicating that they are differently involved in subgroups of LN. Persistent increased levels of IFNλ were associated to an unfavourable HR to treatment.
- Interferon
- Lupus Nephritis
- Systemic Lupus Erythematosus
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Footnotes
Contributors AZ: original idea, patient characterisation, acquisition of data, statistical analyses, interpretation of results and manuscript writing. VO: cytokine measurements, interpretation of results and manuscript writing. IP: patient characterisation and acquisition of data. ES: interpretation of results and manuscript writing. YS: Immunostaining of renal tissue and manuscript writing. IG: original idea, study design, interpretation of results and manuscript writing.
Funding Financial support was provided by grants from the King Gustaf V 80th Birthday Fund, the Karolinska Institute Foundation, the Swedish Association against Rheumatism, the Swedish Medical Research Council and the Swedish Kidney Association and through the regional agreement on medical training and clinical research between the Stockholm County Council and the Karolinska Institute.
Competing interests None.
Ethics approval KI Forskningsetikkommitte Nord, Karolinska sjukhuset; Regionala etikprövningsnämnden i Stockholm.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.