June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Expression kinetics of Glucocorticoid Receptor Isoforms Predicts Treatment Response to Glucocorticoids in Uveitis patients
Author Affiliations & Notes
  • Cristhian A Urzua
    Ophthalmology, Universidad de Chile, Santiago, Chile
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • Han Si
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • Baoying Liu
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • Philippa Lait
    School of clinical sciences, University of Bristol, Bristol, United Kingdom, Bristol, United Kingdom
  • Richard W J Lee
    School of clinical sciences, University of Bristol, Bristol, United Kingdom, Bristol, United Kingdom
  • Annelise Goecke
    Universidad de Chile, Santiago, Chile
  • Robert B Nussenblatt
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • Footnotes
    Commercial Relationships Cristhian Urzua, None; Han Si, None; Baoying Liu, None; Philippa Lait, None; Richard Lee, None; Annelise Goecke, None; Robert Nussenblatt, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 853. doi:
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      Cristhian A Urzua, Han Si, Baoying Liu, Philippa Lait, Richard W J Lee, Annelise Goecke, Robert B Nussenblatt; Expression kinetics of Glucocorticoid Receptor Isoforms Predicts Treatment Response to Glucocorticoids in Uveitis patients. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):853.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Glucocorticoids (GC) have been the mainstay therapy for autoimmue uveitis for decades, but up to one third of patients are unable to achieve disease control at tolerable GC doses, developing vision-threatening complications and requiring immunosuppressive therapy (IMT). Glucocorticoid receptor (GR)-isoforms - including two classical post-transcriptional GR alpha isoform (GRα) and beta isoform (GRβ)- have been implicated in the mechanism of GC resistance. However, the utility of using GR isoforms in uveitis patients, to identify GC resistance, have not been fully investigated. In this study, we evaluate the expression kinetics of GRα and GRβ in peripheral blood mononuclear cells (PBMCs) in uveitis patients, and test whether it can be used to identify GC resistance at an early point.

Methods: Twenty-one systemic treatment naïve autoimmune uveitis patients were recruited. GC resistance was defined as a persistence of active intraocular inflammation, despite of treatment with 1 mg /kg/day of oral prednisone for at least one month. Otherwise, patients were categorized as GC-sensitive. Real-Time qPCR were performed to measure mRNA levels of GR α/β in PBMCs, at baseline and two weeks after prednisone initiation.

Results: There is no significant difference on the expression levels of GRα and GRβ between GC-sensitive and GC-resistant patients at baseline. After two weeks of prednisone treatment, the expression of GRα increased in GC-sensitive patients, while there was a decrease of this isoform in GC-resistant patients (5.5 fold vs 0.7 fold, p=0.01). GRβ expression increased in both groups with a significant higher level in GC-sensitive patients (6.6 fold vs 4.6 fold, p=0.03). The expression levels of GR isoforms were independent of disease activity.

Conclusions: The evaluation of expression kinetics of GR isoforms could potentially serve as a biomarker to early identify GC-resistant uveitis patients. These results contribute to our knowledge in understanding the complex mechanism of GR resistance and may facilitate clinical decision-making in the management of autoimmune uveitis.

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