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High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis
- 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.
- Subjects :
- Chemokine
Immunology
Lupus nephritis
Plasmacytoid dendritic cell
Article
Podocyte
Pathogenesis
Rheumatology
Interferon
Gene expression
medicine
Humans
Lupus Erythematosus, Systemic
Immunology and Allergy
Lectins, C-Type
Receptors, Immunologic
Membrane Glycoproteins
biology
business.industry
medicine.disease
Lupus Nephritis
medicine.anatomical_structure
Antibodies, Antinuclear
Interferon Type I
biology.protein
Antibody
business
medicine.drug
Subjects
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