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High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis.
Iwamoto, Taro; Dorschner, Jessica M; Selvaraj, Shanmugapriya; Mezzano, Valeria; Jensen, Mark A; Vsetecka, Danielle; Amin, Shreyasee; Makol, Ashima; Osborn, Thomas; Moder, Kevin; Chowdhary, Vaidehi R; Izmirly, Peter; Belmont, H Michael; Clancy, Robert M; Buyon, Jill P; Wu, Ming; Loomis, Cynthia A; Niewold, Timothy B.
Afiliação
  • Iwamoto T; T. Iwamoto, MD, PhD, Colton Center for Autoimmunity, New York University, New York, New York, USA, and Allergy and Clinical Immunology, Chiba University, Japan.
  • Dorschner JM; 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.
  • Selvaraj S; 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.
  • Mezzano V; 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.
  • Jensen MA; 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.
  • Vsetecka D; 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.
  • Amin S; 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.
  • Makol A; 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.
  • Osborn T; 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.
  • Moder K; 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.
  • Chowdhary VR; 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.
  • Izmirly P; P. Izmirly, MD, H.M. Belmont, MD, Division of Rheumatology, New York University, New York, New York, USA.
  • Belmont HM; P. Izmirly, MD, H.M. Belmont, MD, Division of Rheumatology, New York University, New York, New York, USA.
  • Clancy RM; 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.
  • Buyon JP; 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.
  • Wu M; 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.
  • Loomis CA; 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.
  • Niewold TB; 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.
J Rheumatol ; 49(4): 388-397, 2022 04.
Article em En | MEDLINE | ID: mdl-34782453
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Nefrite Lúpica / Interferon Tipo I / Lúpus Eritematoso Sistêmico Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Nefrite Lúpica / Interferon Tipo I / Lúpus Eritematoso Sistêmico Idioma: En Ano de publicação: 2022 Tipo de documento: Article