Taro Iwamoto1, Jessica M Dorschner2, Shanmugapriya Selvaraj3, Valeria Mezzano3, Mark A Jensen4, Danielle Vsetecka2, Shreyasee Amin2, Ashima Makol2, Thomas Osborn2, Kevin Moder2, Vaidehi R Chowdhary2, Peter Izmirly5, H Michael Belmont5, Robert M Clancy4, Jill P Buyon4, Ming Wu3, Cynthia A Loomis3, Timothy B Niewold6. 1. T. Iwamoto, MD, PhD, Colton Center for Autoimmunity, New York University, New York, New York, USA, and Allergy and Clinical Immunology, Chiba University, Japan. 2. J.M. Dorschner, BS, D. Vsetecka, MPH, S. Amin, MD, A. Makol, MD, T. Osborn, MD, K. Moder, MD, V.R. Chowdhary, MD, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. 3. S. Selvaraj, MS, V. Mezzano, MD, PhD, M. Wu, MD, C.A. Loomis, MD, PhD, Department of Pathology, New York University, New York, New York, USA. 4. M.A. Jensen, PhD, R.M. Clancy, PhD, J.P. Buyon, MD, T.B. Niewold, MD, Colton Center for Autoimmunity, New York University, New York, New York, USA. 5. P. Izmirly, MD, H.M. Belmont, MD, Division of Rheumatology, New York University, New York, New York, USA. 6. M.A. Jensen, PhD, R.M. Clancy, PhD, J.P. Buyon, MD, T.B. Niewold, MD, Colton Center for Autoimmunity, New York University, New York, New York, USA; Timothy.Niewold@nyulangone.org.
Abstract
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.
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.
Authors: Corinna E Weckerle; Beverly S Franek; Jennifer A Kelly; Marissa Kumabe; Rachel A Mikolaitis; Stephanie L Green; Tammy O Utset; Meenakshi Jolly; Judith A James; John B Harley; Timothy B Niewold Journal: Arthritis Rheum Date: 2011-04
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Authors: Peter M Izmirly; Isabella Wan; Sara Sahl; Jill P Buyon; H Michael Belmont; Jane E Salmon; Anca Askanase; Joan M Bathon; Laura Geraldino-Pardilla; Yousaf Ali; Ellen M Ginzler; Chaim Putterman; Caroline Gordon; Charles G Helmick; Hilary Parton Journal: Arthritis Rheumatol Date: 2017-09-10 Impact factor: 10.995