PT  - JOURNAL ARTICLE
AU  - Taro Iwamoto
AU  - Jessica M. Dorschner
AU  - Shanmugapriya Selvaraj
AU  - Valeria Mezzano
AU  - Mark A. Jensen
AU  - Danielle Vsetecka
AU  - Shreyasee Amin
AU  - Ashima Makol
AU  - Thomas Osborn
AU  - Kevin Moder
AU  - Vaidehi R. Chowdhary
AU  - Peter Izmirly
AU  - H. Michael Belmont
AU  - Robert M. Clancy
AU  - Jill P. Buyon
AU  - Ming Wu
AU  - Cynthia A. Loomis
AU  - Timothy B. Niewold
TI  - High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis
AID  - 10.3899/jrheum.210391
DP  - 2022 Apr 01
TA  - The Journal of Rheumatology
PG  - 388--397
VI  - 49
IP  - 4
4099  - http://www.jrheum.org/content/49/4/388.short
4100  - http://www.jrheum.org/content/49/4/388.full
SO  - J Rheumatol2022 Apr 01; 49
AB  - Objective Previous studies suggest a link between high serum type I interferon (IFN) and lupus nephritis (LN). We determined whether serum IFN activity is associated with subtypes of LN and studied renal tissues and cells to understand the effect of IFN in LN.Methods Two hundred and twenty-one patients with systemic lupus erythematosus were studied. Serum IFN activity was measured by WISH bioassay. mRNA in situ hybridization was used in renal tissue to measure expression of the representative IFN-induced gene, IFN-induced protein with tetratricopeptide repeats-1 (IFIT1), and the plasmacytoid dendritic cell (pDC) marker gene C-type lectin domain family-4 member C (CLEC4C). Podocyte cell line gene expression was measured by real-time PCR.Results Class III/IV LN prevalence was significantly increased in patients with high serum IFN compared with those with low IFN (odds ratio 5.40, P = 0.009). In multivariate regression models, type I IFN was a stronger predictor of class III/IV LN than complement C3 or anti-dsDNA antibody, and could account for the association of these variables with LN. IFIT1 expression was increased in all classes of LN, but most in the glomerular areas of active class III/IV LN kidneys. IFIT1 expression was not closely colocalized with pDCs. IFN directly activated podocyte cell lines to induce chemokines and proapoptotic molecules.Conclusion Systemic high IFN is involved in the pathogenesis of severe LN. We did not find colocalization of 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.