Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus ErythematosusCitation formats

  • External authors:
  • Jie An
  • Laura Durcan
  • Reynold M. Karr
  • Thomas H. Teal
  • Joshua J. Woodward
  • Keith B. Elkon

Standard

Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus. / An, Jie; Durcan, Laura; Karr, Reynold M.; Briggs, Tracy A.; Rice, Gillian I.; Teal, Thomas H.; Woodward, Joshua J.; Elkon, Keith B.

In: Arthritis & rheumatology (Hoboken, N.J.), Vol. 69, No. 4, 04.2017, p. 800-807.

Research output: Contribution to journalArticle

Harvard

An, J, Durcan, L, Karr, RM, Briggs, TA, Rice, GI, Teal, TH, Woodward, JJ & Elkon, KB 2017, 'Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus', Arthritis & rheumatology (Hoboken, N.J.), vol. 69, no. 4, pp. 800-807. https://doi.org/10.1002/art.40002

APA

An, J., Durcan, L., Karr, R. M., Briggs, T. A., Rice, G. I., Teal, T. H., ... Elkon, K. B. (2017). Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus. Arthritis & rheumatology (Hoboken, N.J.), 69(4), 800-807. https://doi.org/10.1002/art.40002

Vancouver

An J, Durcan L, Karr RM, Briggs TA, Rice GI, Teal TH et al. Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus. Arthritis & rheumatology (Hoboken, N.J.). 2017 Apr;69(4):800-807. https://doi.org/10.1002/art.40002

Author

An, Jie ; Durcan, Laura ; Karr, Reynold M. ; Briggs, Tracy A. ; Rice, Gillian I. ; Teal, Thomas H. ; Woodward, Joshua J. ; Elkon, Keith B. / Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus. In: Arthritis & rheumatology (Hoboken, N.J.). 2017 ; Vol. 69, No. 4. pp. 800-807.

Bibtex

@article{fff776c57b9a43368266e9ae1ddd866c,
title = "Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus",
abstract = "Objective Type I interferon (IFN) is implicated in the pathogenesis of systemic lupus erythematosus (SLE) and interferonopathies such as Aicardi‐Gouti{\`e}res syndrome. A recently discovered DNA‐activated type I IFN pathway, cyclic GMP‐AMP synthase (cGAS), has been linked to Aicardi‐Gouti{\`e}res syndrome and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to type I IFN production in patients with SLE. Methods SLE disease activity was measured by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index. Expression of messenger RNA for cGAS and IFN‐stimulated genes (ISGs) was determined by quantitative polymerase chain reaction analysis. Cyclic GMP‐AMP (cGAMP) levels were examined by multiple reaction monitoring with ultra‐performance liquid chromatography tandem mass spectrometry. Results Expression of cGAS in peripheral blood mononuclear cells (PBMCs) was significantly higher in SLE patients than in normal controls (n = 51 and n = 20 respectively; P < 0.01). There was a positive correlation between cGAS expression and the IFN score (P < 0.001). The expression of cGAS in PBMCs showed a dose response to type I IFN stimulation in vitro, consistent with it being an ISG. Targeted measurement of cGAMP by tandem mass spectrometry detected cGAMP in 15{\%} of the SLE patients (7 of 48) but none of the normal (0 of 19) or rheumatoid arthritis (0 of 22) controls. Disease activity was higher in SLE patients with cGAMP versus those without cGAMP. Conclusion Increased cGAS expression and cGAMP in a proportion of SLE patients indicates that the cGAS pathway should be considered as a contributor to type I IFN production. Whereas higher cGAS expression may be a consequence of exposure to type I IFN, detection of cGAMP in patients with increased disease activity indicates potential involvement of this pathway in disease expression.",
author = "Jie An and Laura Durcan and Karr, {Reynold M.} and Briggs, {Tracy A.} and Rice, {Gillian I.} and Teal, {Thomas H.} and Woodward, {Joshua J.} and Elkon, {Keith B.}",
note = "{\circledC} 2016, American College of Rheumatology.",
year = "2017",
month = "4",
doi = "10.1002/art.40002",
language = "English",
volume = "69",
pages = "800--807",
journal = "Arthritis & Rheumatology (Hoboken)",
issn = "2326-5191",
publisher = "John Wiley & Sons Ltd",
number = "4",

}

RIS

TY - JOUR

T1 - Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus

AU - An, Jie

AU - Durcan, Laura

AU - Karr, Reynold M.

AU - Briggs, Tracy A.

AU - Rice, Gillian I.

AU - Teal, Thomas H.

AU - Woodward, Joshua J.

AU - Elkon, Keith B.

N1 - © 2016, American College of Rheumatology.

PY - 2017/4

Y1 - 2017/4

N2 - Objective Type I interferon (IFN) is implicated in the pathogenesis of systemic lupus erythematosus (SLE) and interferonopathies such as Aicardi‐Goutières syndrome. A recently discovered DNA‐activated type I IFN pathway, cyclic GMP‐AMP synthase (cGAS), has been linked to Aicardi‐Goutières syndrome and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to type I IFN production in patients with SLE. Methods SLE disease activity was measured by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index. Expression of messenger RNA for cGAS and IFN‐stimulated genes (ISGs) was determined by quantitative polymerase chain reaction analysis. Cyclic GMP‐AMP (cGAMP) levels were examined by multiple reaction monitoring with ultra‐performance liquid chromatography tandem mass spectrometry. Results Expression of cGAS in peripheral blood mononuclear cells (PBMCs) was significantly higher in SLE patients than in normal controls (n = 51 and n = 20 respectively; P < 0.01). There was a positive correlation between cGAS expression and the IFN score (P < 0.001). The expression of cGAS in PBMCs showed a dose response to type I IFN stimulation in vitro, consistent with it being an ISG. Targeted measurement of cGAMP by tandem mass spectrometry detected cGAMP in 15% of the SLE patients (7 of 48) but none of the normal (0 of 19) or rheumatoid arthritis (0 of 22) controls. Disease activity was higher in SLE patients with cGAMP versus those without cGAMP. Conclusion Increased cGAS expression and cGAMP in a proportion of SLE patients indicates that the cGAS pathway should be considered as a contributor to type I IFN production. Whereas higher cGAS expression may be a consequence of exposure to type I IFN, detection of cGAMP in patients with increased disease activity indicates potential involvement of this pathway in disease expression.

AB - Objective Type I interferon (IFN) is implicated in the pathogenesis of systemic lupus erythematosus (SLE) and interferonopathies such as Aicardi‐Goutières syndrome. A recently discovered DNA‐activated type I IFN pathway, cyclic GMP‐AMP synthase (cGAS), has been linked to Aicardi‐Goutières syndrome and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to type I IFN production in patients with SLE. Methods SLE disease activity was measured by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index. Expression of messenger RNA for cGAS and IFN‐stimulated genes (ISGs) was determined by quantitative polymerase chain reaction analysis. Cyclic GMP‐AMP (cGAMP) levels were examined by multiple reaction monitoring with ultra‐performance liquid chromatography tandem mass spectrometry. Results Expression of cGAS in peripheral blood mononuclear cells (PBMCs) was significantly higher in SLE patients than in normal controls (n = 51 and n = 20 respectively; P < 0.01). There was a positive correlation between cGAS expression and the IFN score (P < 0.001). The expression of cGAS in PBMCs showed a dose response to type I IFN stimulation in vitro, consistent with it being an ISG. Targeted measurement of cGAMP by tandem mass spectrometry detected cGAMP in 15% of the SLE patients (7 of 48) but none of the normal (0 of 19) or rheumatoid arthritis (0 of 22) controls. Disease activity was higher in SLE patients with cGAMP versus those without cGAMP. Conclusion Increased cGAS expression and cGAMP in a proportion of SLE patients indicates that the cGAS pathway should be considered as a contributor to type I IFN production. Whereas higher cGAS expression may be a consequence of exposure to type I IFN, detection of cGAMP in patients with increased disease activity indicates potential involvement of this pathway in disease expression.

U2 - 10.1002/art.40002

DO - 10.1002/art.40002

M3 - Article

VL - 69

SP - 800

EP - 807

JO - Arthritis & Rheumatology (Hoboken)

JF - Arthritis & Rheumatology (Hoboken)

SN - 2326-5191

IS - 4

ER -