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

Abstract 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 phytohemagglutini...

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Main Authors: 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
Format: Article
Language:English
Published: BMC 2017-08-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13075-017-1404-z
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author 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
author_facet 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
author_sort Sung Soo Ahn
collection DOAJ
description Abstract 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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spelling doaj.art-ed14a0506f3745068386b22d19f85e4f2022-12-21T18:37:40ZengBMCArthritis Research & Therapy1478-63622017-08-011911910.1186/s13075-017-1404-zDecreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupusSung Soo Ahn0Eun Seong Park1Joo Sung Shim2Sang-Jun Ha3Beom Seok Kim4Seung Min Jung5Sang-Won Lee6Yong-Beom Park7Jason Jungsik Song8Division of Rheumatology, Department of Internal Medicine, Yonsei University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Yonsei University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Yonsei University College of MedicineDepartment of Biochemistry, College of Life Science & Biotechnology, Yonsei UniversityDivision of Nephrology, Department of Internal Medicine, Yonsei University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Yonsei University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Yonsei University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Yonsei University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Yonsei University College of MedicineAbstract 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.http://link.springer.com/article/10.1186/s13075-017-1404-zIFN-γ releasing assayIFN-γSystemic lupus erythematosusT cell
spellingShingle 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
Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus
Arthritis Research & Therapy
IFN-γ releasing assay
IFN-γ
Systemic lupus erythematosus
T cell
title Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus
title_full Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus
title_fullStr Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus
title_full_unstemmed Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus
title_short Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus
title_sort decreased ex vivo production of interferon gamma is associated with severity and poor prognosis in patients with lupus
topic IFN-γ releasing assay
IFN-γ
Systemic lupus erythematosus
T cell
url http://link.springer.com/article/10.1186/s13075-017-1404-z
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