PMID- 34782453
OWN - NLM
STAT- MEDLINE
DCOM- 20220405
LR  - 20230402
IS  - 1499-2752 (Electronic)
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
VI  - 49
IP  - 4
DP  - 2022 Apr
TI  - High Systemic Type I Interferon Activity Is Associated With Active Class III/IV 
      Lupus Nephritis.
PG  - 388-397
LID - 10.3899/jrheum.210391 [doi]
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.
CI  - Copyright (c) 2022 by the Journal of Rheumatology.
FAU - Iwamoto, Taro
AU  - Iwamoto T
AUID- ORCID: 0000-0003-1663-3518
AD  - T. Iwamoto, MD, PhD, Colton Center for Autoimmunity, New York University, New 
      York, New York, USA, and Allergy and Clinical Immunology, Chiba University, 
      Japan.
FAU - Dorschner, Jessica M
AU  - Dorschner JM
AD  - 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.
FAU - Selvaraj, Shanmugapriya
AU  - Selvaraj S
AD  - 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.
FAU - Mezzano, Valeria
AU  - Mezzano V
AD  - 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.
FAU - Jensen, Mark A
AU  - Jensen MA
AD  - 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.
FAU - Vsetecka, Danielle
AU  - Vsetecka D
AD  - 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.
FAU - Amin, Shreyasee
AU  - Amin S
AD  - 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.
FAU - Makol, Ashima
AU  - Makol A
AD  - 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.
FAU - Osborn, Thomas
AU  - Osborn T
AD  - 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.
FAU - Moder, Kevin
AU  - Moder K
AD  - 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.
FAU - Chowdhary, Vaidehi R
AU  - Chowdhary VR
AD  - 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.
FAU - Izmirly, Peter
AU  - Izmirly P
AD  - P. Izmirly, MD, H.M. Belmont, MD, Division of Rheumatology, New York University, 
      New York, New York, USA.
FAU - Belmont, H Michael
AU  - Belmont HM
AD  - P. Izmirly, MD, H.M. Belmont, MD, Division of Rheumatology, New York University, 
      New York, New York, USA.
FAU - Clancy, Robert M
AU  - Clancy RM
AD  - 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.
FAU - Buyon, Jill P
AU  - Buyon JP
AD  - 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.
FAU - Wu, Ming
AU  - Wu M
AD  - 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.
FAU - Loomis, Cynthia A
AU  - Loomis CA
AD  - 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.
FAU - Niewold, Timothy B
AU  - Niewold TB
AD  - 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.
LA  - eng
GR  - R01 AR057781/AR/NIAMS NIH HHS/United States
GR  - R01 AR060861/AR/NIAMS NIH HHS/United States
GR  - R01 AR065964/AR/NIAMS NIH HHS/United States
GR  - R21 AR078416/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211115
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (CLEC4C protein, human)
RN  - 0 (Interferon Type I)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (anti-dsDNA autoantibody)
SB  - IM
MH  - Antibodies, Antinuclear
MH  - Humans
MH  - *Interferon Type I
MH  - Lectins, C-Type
MH  - *Lupus Erythematosus, Systemic
MH  - *Lupus Nephritis/pathology
MH  - Membrane Glycoproteins
MH  - Receptors, Immunologic
PMC - PMC8977285
MID - NIHMS1754241
OTO - NOTNLM
OT  - interferon signature gene
OT  - lupus nephritis
OT  - podocyte injury type I interferon
EDAT- 2021/11/17 06:00
MHDA- 2022/04/06 06:00
PMCR- 2023/04/01
CRDT- 2021/11/16 06:13
PHST- 2021/11/03 00:00 [accepted]
PHST- 2021/11/17 06:00 [pubmed]
PHST- 2022/04/06 06:00 [medline]
PHST- 2021/11/16 06:13 [entrez]
PHST- 2023/04/01 00:00 [pmc-release]
AID - jrheum.210391 [pii]
AID - 10.3899/jrheum.210391 [doi]
PST - ppublish
SO  - J Rheumatol. 2022 Apr;49(4):388-397. doi: 10.3899/jrheum.210391. Epub 2021 Nov 
      15.