Potential involvement of IL-40 in kidney disease associated to systemic lupus erythematosus

Abstract

Objectives: Aim of this study was to investigate the expression of interleukin (IL)-40, a cytokine associated with B cells homoeostasis and immune response, in Systemic lupus erythematosus (SLE) and SLE associated nephritis. Methods: 32 patients with SLE and 21 controls were enrolled. Serum concentration of IL-40 was assessed by ELISA and cellular sources of IL-40 were determined by flow-cytometry. An in vitro assay with recombinant IL-40 (rIL-40) was performed to detect the effect on cytokine production from peripheral blood mononuclear cells (PBMC). In kidney biopsies obtained from patients with lupus nephritis (LN) immunofluorescence was performed to assess IL-40 expression and detect its cellular sources at tissue level. Results: Serum IL-40 levels show a decreasing trend in SLE with LN, compared with SLE without LN and controls. No differences between SLE and controls were evidenced in urinary IL-40 levels; in the percentage of CD3+IL40+, CD19+IL40+ and CD14+IL40+; and in the production of pro-inflammatory cytokines by PBMC stimulated with rIL-40. IL-40 expression was markedly increased in kidney tissue from LN patients, with a significant increase of IL40+ cells in LN samples compared to controls, as confirmed by the quantification analysis. Conclusion: To the best of our knowledge this is the first demonstration of IL-40 expression at kidney level in SLE. These preliminary data suggest a possible role of IL-40 in LN. In particular, IL-40 could be a marker of kidney tissue damage, although its specific mechanism of action needs to be further elucidated.