Higher activation of the interferon-gamma signaling pathway in systemic lupus erythematosus patients with a high type I IFN score: relation to disease activity

Original Article
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Abstract

Increased IFN-γ levels have been associated with systemic lupus erythematosus (SLE). However, the relationships among IFN-γ, type I interferons (IFNs) and clinical features have not been extensively studied. Peripheral blood samples from 44 SLE patients and 36 healthy donors (HDs) were collected. Quantitative real-time PCR was used to assess the mRNA expression of IFNG, type II IFN-inducible genes (IRF1, GBP1, CXCL9, CXCL10, and SERPING1, which are used for the type II IFN score), type I IFN-inducible genes (IRF7, MX1, ISG15, and ISG20, which are used for the type I IFN score), TBX21, and EOMES in peripheral blood mononuclear cells. Flow cytometry was used to measure the IFN-γ levels in lymphocytes. The mRNA levels of type II IFN-inducible genes, IFNG, TBX21, and EOMES were significantly higher in SLE patients than those in HDs. Similarly, the percentages of IFN-γ-producing cells in lymphocytes and their subsets in SLE patients were significantly increased. Linear regression indicated that IFNG expression levels and type II IFN scores were positively correlated with anti-double-stranded DNA autoantibody levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. Compared with patients with low type I IFN scores, patients with high type I IFN scores showed increased type II IFN scores and SLEDAI scores. Type II IFN scores were positively associated with type I IFN scores. The IFN-γ signaling pathway is activated in SLE patients and may be considered an index of disease activity. IFN-γ, together with type I IFNs, promotes the pathogenesis of SLE.

Keywords

Disease activity EOMES Interferon-gamma Interferon-inducible genes Systemic lupus erythematosus TBX21 

Notes

Acknowledgments

This research was supported by the grants from the National Natural Science Foundation of China (31470854) and Pujiang Talents Plan (16PJ1405600).

Funding information

National Natural Science Foundation of China (Grants No. 31470854) and Pujiang Talents Plan (Grants No. 16PJ1405600).

Compliance with ethical standards

The study was approved by the Ethics Committee of Xin Hua Hospital and was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants.

Disclosures

None.

Supplementary material

10067_2018_4138_MOESM1_ESM.docx (16 kb)
Table S1 Primers for real-time PCR (DOCX 15 kb)
10067_2018_4138_Fig6_ESM.jpg (53 kb)
Fig. S1

Comparisons of IFNG expression and IFN-II scores in SLE patients according to LN. IFNG expression (a) and IFN-II scores (b) were not significantly different between inactive LN and active LN patients. (JPG 53 kb)

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10067_2018_4138_Fig7_ESM.jpg (49 kb)
Fig. S2

Positive correlation of IFNG expression with IFN-I scores in SLE patients. Patients with high IFN-I scores(n=32) showed significantly higher IFNG expression than those with low IFN-I scores(n=10) (a). The IFNG expression (b) was positively correlated with IFN-I scores in SLE patients (n=42). (JPG 48 kb)

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10067_2018_4138_Fig8_ESM.jpg (56 kb)
Fig. S3

IFNG expression levels, IFN-II scores and IFN-I scores in SLE patients before and after treatment or follow-up. Data from the same patient before and after treatment or follow-up was denoted by an individual line. SLE patients (n=7) displayed significantly reduced IFNG expression levels (a), IFN-II scores (b) and IFN-I scores (c) after treatment or follow-up. (JPG 55 kb)

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High resolution image (EPS 1864 kb)

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Manman Liu
    • 1
  • Junli Liu
    • 2
  • Shumeng Hao
    • 2
  • Ping Wu
    • 1
  • Xiaoyan Zhang
    • 1
  • Yichuan Xiao
    • 2
  • Gengru Jiang
    • 1
  • Xinfang Huang
    • 1
  1. 1.Department of Renal and RheumatologyXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina

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