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, YongBeom Park, Jason Jungsik Song

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Article number193
JournalArthritis Research and Therapy
Volume19
Issue number1
DOIs
Publication statusPublished - 2017 Aug 25

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Interferon-gamma
Systemic Lupus Erythematosus
Phytohemagglutinins
Mitogens
Hospitalization
Adaptive Immunity
Hospital Mortality
Innate Immunity
Intensive Care Units
Blood Cells
Tuberculosis
Biomarkers

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Ahn, Sung Soo ; Park, Eun Seong ; Shim, Joo Sung ; Ha, Sang-Jun ; Kim, Beom Seok ; Jung, Seung Min ; Lee, Sang Won ; Park, YongBeom ; Song, Jason Jungsik. / Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus. In: Arthritis Research and Therapy. 2017 ; Vol. 19, No. 1.
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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.",
author = "Ahn, {Sung Soo} and Park, {Eun Seong} and Shim, {Joo Sung} and Sang-Jun Ha and Kim, {Beom Seok} and Jung, {Seung Min} and Lee, {Sang Won} and YongBeom Park and Song, {Jason Jungsik}",
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Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus. / Ahn, Sung Soo; Park, Eun Seong; Shim, Joo Sung; Ha, Sang-Jun; Kim, Beom Seok; Jung, Seung Min; Lee, Sang Won; Park, YongBeom; Song, Jason Jungsik.

In: Arthritis Research and Therapy, Vol. 19, No. 1, 193, 25.08.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus

AU - Ahn, Sung Soo

AU - Park, Eun Seong

AU - Shim, Joo Sung

AU - Ha, Sang-Jun

AU - Kim, Beom Seok

AU - Jung, Seung Min

AU - Lee, Sang Won

AU - Park, YongBeom

AU - Song, Jason Jungsik

PY - 2017/8/25

Y1 - 2017/8/25

N2 - 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.

AB - 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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