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

 Sung Soo Ahn  ;  Eun Seong Park  ;  Joo Sung Shim  ;  Sang-Jun Ha  ;  Beom Seok Kim  ;  Seung Min Jung  ;  Sang-Won Lee  ;  Yong-Beom Park  ;  Jason Jungsik Song 
 Arthritis Research & Therapy, Vol.19(1) : 193, 2017 
Journal Title
 Arthritis Research & Therapy 
Issue Date
IFN-γ ; IFN-γ releasing assay ; Systemic lupus erythematosus ; T cell
BACKGROUND: Lupus 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. METHODS: This 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. RESULTS: The 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. CONCLUSIONS: Ex vivo IFN-γ production is a useful biomarker for assessing disease activity and predicting poor clinical outcomes of SLE.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김범석(Kim, Beom Seok) ORCID logo https://orcid.org/0000-0002-5732-2583
박용범(Park, Yong Beom)
박은성(Park, Eun Seong )
송정식(Song, Jungsik Jason) ORCID logo https://orcid.org/0000-0003-0662-7704
안성수(Ahn, Sung Soo) ORCID logo https://orcid.org/0000-0002-9002-9880
이상원(Lee, Sang Won) ORCID logo https://orcid.org/0000-0002-8038-3341
정승민(Jung, Seung Min ) ORCID logo https://orcid.org/0000-0003-3465-2181
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