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Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus

Authors
  • Ahn, Sung Soo1
  • Park, Eun Seong1
  • Shim, Joo Sung1
  • Ha, Sang-Jun2
  • Kim, Beom Seok3
  • Jung, Seung Min1
  • Lee, Sang-Won1
  • Park, Yong-Beom1
  • Song, Jason Jungsik1, 4
  • 1 Yonsei University College of Medicine, Division of Rheumatology, Department of Internal Medicine, 50-1 Yonsei-ro, Seodaemun–gu, Seoul, 03722, South Korea , Seoul (South Korea)
  • 2 Yonsei University, Department of Biochemistry, College of Life Science & Biotechnology, Seoul, South Korea , Seoul (South Korea)
  • 3 Yonsei University College of Medicine, Division of Nephrology, Department of Internal Medicine, Seoul, South Korea , Seoul (South Korea)
  • 4 Yonsei University College of Medicine, Institute for Immunology and Immunological Diseases, Seoul, South Korea , Seoul (South Korea)
Type
Published Article
Journal
Arthritis Research & Therapy
Publisher
Springer Science and Business Media LLC
Publication Date
Aug 25, 2017
Volume
19
Issue
1
Identifiers
DOI: 10.1186/s13075-017-1404-z
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundLupus pathogenesis is closely associated with interferon gamma (IFN-γ), which plays a central role in innate and adaptive immunity. The aim of this study was to evaluate the ex vivo production of IFN-γ after stimulation of peripheral blood mononuclear cells with phytohemagglutinin (PHA) in patients with lupus, according to disease activity.MethodsThis study included 118 patients with lupus who had undergone IFN-γ-releasing assays (IGRAs) to screen for tuberculosis. Data on IFN-γ production in negative (nil) and positive (mitogen with PHA) controls were collected and analysed. The difference (mitogen minus nil) was used to calculate ex vivo IFN-γ production. Disease activity was evaluated using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Poor hospitalisation outcome was defined as in-hospital mortality or intensive care unit admission. Associations among disease activity, poor hospitalisation outcome, and ex vivo IFN-γ production were assessed.ResultsThe level of ex vivo IFN-γ production was significantly lower in patients with active systemic lupus erythematosus (SLE) (n = 64) than in those with inactive SLE (n = 54) (median 0.92 vs. 11.06 IU/mL, p < 0.001). Ex vivo IFN-γ production was correlated with the SLEDAI-2 K (r = − 0.587, p < 0.001). Results of multivariate logistic regression analysis showed that ex vivo IFN-γ production ≤ 7.19 IU/mL was an independent predictor for discriminating active and inactive lupus. In addition, patients with ex vivo IFN-γ production ≤ 0.40 IU/mL had more frequent poor hospitalisation outcomes than those with ex vivo IFN-γ production > 0.40 (40.0% vs. 9.3%, p = 0.001). The proportion of indeterminate IGRA results was higher in patients with active lupus than in those with inactive lupus (45.3% vs. 0.0%, p < 0.001) because of decreased ex vivo IFN-γ production.ConclusionsEx vivo IFN-γ production is a useful biomarker for assessing disease activity and predicting poor clinical outcomes of SLE.

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