High systemic IFN activity tied to class III/IV lupus nephritis

High systemic type I interferon (IFN) activity plays a significant role in the pathogenesis of severe lupus nephritis (LN), according to a recent study.

“We did not find colocalization of plasmacytoid dendritic cell (pDCs) with IFN signature in renal tissue, and instead observed the greatest intensity of the IFN signature in glomerular areas, which could suggest a blood source of IFN,” the authors said.

This study included 221 patients with systemic lupus erythematosus. The authors measured serum IFN activity using WISH bioassay. In addition, they applied mRNA in situ hybridization to measure expression of the representative IFN-induced gene, IFN-induced protein with tetratricopeptide repeats-1 (IFIT1), and the pDC marker gene C-type lectin domain family-4 member C (CLEC4C). Real-time PCR was then used to measure podocyte cell line gene expression.

Patients with high serum IFN had significant higher prevalence of class III/IV LN than those with low IFN (odds ratio, 5.40; p=0.009). In multivariate regression models, type 1 IFN was a better predictor of class III/IV LN than complement C3 or anti-dsDNA antibody; it also accounted for the association of these variables with LN.

IFIT1 expression was elevated in all LN classes, but mostly in the glomerular areas of active class III/IV LN kidneys, and was not closely colocalized with pDCs. Notably, IFN directly activated podocyte cell lines to stimulate chemokines and proapoptotic molecules.

“Previous studies suggest a link between high serum type I IFN and LN,” the authors said.