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High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis

Authors :
Cynthia A. Loomis
Robert R. Clancy
Jill P. Buyon
Danielle M. Vsetecka
Ashima Makol
Peter M. Izmirly
Taro Iwamoto
H. Michael Belmont
Vaidehi R. Chowdhary
T G Osborn
Kevin G. Moder
Shreyasee Amin
Jessica M. Dorschner
Shanmugapriya Selvaraj
Valeria Mezzano
Mark A. Jensen
Ming Wu
Timothy B. Niewold
Source :
J Rheumatol
Publication Year :
2021
Publisher :
The Journal of Rheumatology, 2021.

Abstract

ObjectivePrevious 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.MethodsTwo 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.ResultsClass 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.ConclusionSystemic 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.

Details

ISSN :
14992752 and 0315162X
Volume :
49
Database :
OpenAIRE
Journal :
The Journal of Rheumatology
Accession number :
edsair.doi.dedup.....f202cdb0ac3764a72f2d53891f9927e9
Full Text :
https://doi.org/10.3899/jrheum.210391