Background/purpose Lupus nephritis (LN) is one of the most severe types of organ involvement in systemic lupus erythematosus (SLE), despite the recent advances in immunosuppressive therapies. High type 1 interferon (IFN) is a heritable risk for SLE, and some previous studies have suggested a link between high IFN and lupus nephritis. However, little is known about the relationships between high levels of IFN and the subtypes of LN, and whether IFN is more associated with anti-dsDNA antibodies or with clinical nephritis.

Methods We studied 244 European-American (EA) SLE patients and measured type 1 IFN in sera by performing WISH IFN bioassay as described previously. Subtypes of LN were confirmed by renal biopsy review. Complements, anti-dsDNA and other auto-antibodies were measured in the clinical laboratory, and standard clinical cut-offs were used to define a positive result. Non-parametric analyses were used to compare IFN data with the clinical data.

Results IFN level and SLEDAI score was positively correlated (r=0.26, p<0.0001, Spearman) in our cross-sectional evaluation. EA subjects with a high levels of IFN (IFN score >2) were more likely to have renal manifestations compared to the subjects with a low levels of IFN (IFN score <2) (p<0.001, OR=3.0, Fisher’s exact test). In addition, the incidence rate of class 3/4 LN was significantly higher among patients with a high levels of IFN compared to the patients with low levels of IFN (p<0.01, OR=5.5, Fisher’s exact test). Notably, IFN level was significantly higher in active class 3/4 LN compared to inactive class 3/4 LN (p<0.05 Mann-Whitney U) and this was not observed in non-class 3/4 LN populations. Positivity of ds-DNA antibody did not show significant difference between inactive class 3/4 LN and active class 3/4 LN.

Conclusion Our data support an association between type 1 IFN and class 3/4 nephritis that is independent of overall SLEDAI and anti-dsDNA antibodies, suggesting that IFN is involved in renal pathogenesis. These data also suggest that IFN could predict renal disease activity or the future risk of developing LN, especially class 3/4 LN in EA SLE patients.