Background/Purpose: Despite recent advancements in immunosuppressive therapies, lupus nephritis (LN) remains one of the most severe organ manifestations in systemic lupus erythematosus (SLE). High type I interferon (IFN) is a heritable risk for SLE, and 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 plays a critical role in the pathogenesis of LN.

Methods: We studied 221 European-American SLE patients and measured IFN in sera by performing WISH IFN bioassay as described previously. Subtypes of LN were confirmed by renal biopsy review. Complement, anti-dsDNA and other serological parameters were measured in the clinical laboratory, and standard clinical cut-offs were used to define a positive result. mRNA in situ hybridization was performed to detect IFN induced gene (IIG) expression and plasmacytoid dendritic cells in LN kidney biopsies, and Visiopharm analysis software was used for quantitative analysis. Real-time PCR was performed to measure pro-apoptotic gene expressions in human podocyte cell lines. Non-parametric analyses were used unless otherwise mentioned.

Results: Proliferative LN was significantly more common among patients with high serum type I IFN compared to patients with low levels of IFN (p<0.001, OR=3.0, Fisher’s exact test). Notably, IFN level was significantly higher in active proliferative LN compared to inactive proliferative LN (p<0.001), and these findings were independent of complements and anti-dsDNA antibody levels. mRNA in situ hybridization showed increased expression of IIG accompanying plasmacytoid dendritic cell infiltration in active proliferative LN kidneys. In vitro experiments demonstrated that type I IFN induced pro-apoptotic gene expression in human podocyte cell lines.

Conclusion: Our data support an association between type I IFN and active proliferative lupus nephritis that is independent of conventional parameters such as complements 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 proliferative LN in SLE patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-high-type-i-interferon-is-associated-with-active-proliferative-lupus-nephritis-in-lupus-patients-accompanied-with-high-interferon-signature-gene-expression-and-plasmacytoid-dendritic-cell-infilt/