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The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice
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Systemic sclerosis and lupus: points in an interferon-mediated continuum.

Shervin Assassi1, Maureen D Mayes, Frank C Arnett

  • 1University of Texas Health Science Center, Houston, TX, USA. shervin.assassi@uth.tmc.edu

Arthritis and Rheumatism
|January 30, 2010
PubMed
Summary

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) share a spectrum of interferon (IFN)-mediated disease, with SSc patients exhibiting a lupus-like IFN gene expression pattern linked to specific antibodies.

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Area of Science:

  • Immunology
  • Genetics
  • Rheumatology

Background:

  • Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are autoimmune diseases with distinct clinical manifestations.
  • Understanding shared molecular pathways, such as interferon (IFN) signaling, is crucial for disease classification and treatment.

Purpose of the Study:

  • To compare peripheral blood (PB) cell transcript profiles in SSc and SLE patients.
  • To investigate the role of IFN-inducible genes in SSc and SLE pathogenesis.
  • To correlate IFN gene expression with clinical and serological subtypes in SSc.

Main Methods:

  • Analysis of PB cell samples from 74 SSc patients, 17 SLE patients, and 21 healthy controls.
  • Gene expression profiling using Illumina Human Ref-8 BeadChips and quantitative PCR.
  • Calculation of a composite score for IFN-inducible genes and correlation with clinical/serological data.

Main Results:

  • Both SSc and SLE showed prominent overexpression of IFN-inducible genes in PB cells.
  • A significant overlap (91%) in upregulated IFN-inducible genes was observed between SSc and SLE.
  • IFN scores were significantly higher in SLE and SSc patients compared to controls, with SLE having the highest score.

Conclusions:

  • SLE and SSc represent a spectrum of IFN-mediated autoimmune diseases.
  • A subset of SSc patients displays a 'lupus-like' IFN gene expression profile.
  • This 'lupus-like' pattern in SSc correlates with antitopoisomerase and anti-U1 RNP antibodies and lymphopenia.