Interferon (IFN)-λ is a potential mediator in lupus nephritis

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.

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.

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.

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.