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

Objectives: Interferon (IFN)-alpha is thought to be central in the pathogenesis for lupus nephritis (LN) and recent studies also indicate a role for IFN lambda. Little is known about these cytokines in the context of treatment response. We studied levels of IFN alpha and IFN lambda 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 IFN alpha and IFN lambda 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 IFN lambda in renal tissue was assessed by immunohistochemistry. Results: At baseline, serum levels of both IFN alpha and IFN lambda were higher in patients versus controls (p=0.01 and p=0.03, respectively). There was no correlation between IFN alpha and IFN lambda. Overall, IFN alpha decreased after treatment (p=0.003) but IFN lambda remained unchanged. However in patients with HR, IFNX decreased (p=0.01). The highest levels of IFN lambda were seen in patients with poor HR. Immunostaining of renal tissue revealed expression of IFN lambda, particularly in crescent formations, inflammatory infiltrates and tubular cells. Conclusions: The study supports a role for IFN lambda in LN, both in circulation and at a tissue level. Levels of IFN alpha and IFN lambda did not correlate and were affected differently by immunosuppression, indicating that they are differently involved in subgroups of LN. Persistent increased levels of IFN lambda were associated to an unfavourable HR to treatment.