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Open Access Research article

In vitro glucocorticoid sensitivity is associated with clinical glucocorticoid therapy outcome in rheumatoid arthritis

Rogier AM Quax1*, Jan W Koper1, Pascal HP de Jong2, Ramona van Heerebeek1, Angelique E Weel3, Anne M Huisman4, Derkjen van Zeben4, Frank H de Jong1, Steven WJ Lamberts1, Johanna MW Hazes2 and Richard A Feelders1

Author Affiliations

1 Department of Internal Medicine, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, Rotterdam, 3015 CE, The Netherlands

2 Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, Rotterdam, 3015 CE, The Netherlands

3 Department of Rheumatology, Maasstad Hospital, Maasstadweg 21, Rotterdam, 3079DZ, The Netherlands

4 Department of Rheumatology, Sint Franciscus Gasthuis, Kleiweg 500, Rotterdam, 3045PM, The Netherlands

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Arthritis Research & Therapy 2012, 14:R195  doi:10.1186/ar4029

Published: 24 August 2012

Abstract

Introduction

Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). In clinical practice, GC treatment is not adapted to these differences in GC sensitivity. In vitro assessment of GC sensitivity before the start of therapy could allow more individualized GC therapy. The aim of the study was to investigate the association between in vitro and in vivo GC sensitivity in RA.

Methods

Thirty-eight early and 37 established RA patients were prospectively studied. In vitro GC sensitivity was assessed with dexamethasone-induced effects on interleukin-2 (IL-2) and glucocorticoid-induced leucine zipper (GILZ) messenger RNA expression in peripheral blood mononuclear cells (PBMCs). A whole-cell dexamethasone-binding assay was used to measure number and affinity (1/KD) of glucocorticoid receptors (GRs).

In vivo GC sensitivity was determined by measuring the disease activity score (DAS) and health assessment questionnaire disability index (HAQ-DI) score before and after 2 weeks of standardized GC treatment.

Results

GR number was positively correlated with improvement in DAS. IL-2-EC50 and GILZ-EC50 values both had weak near-significant correlations with clinical improvement in DAS in intramuscularly treated patients only. HAQ responders had lower GILZ-EC50 values and higher GR number and KD.

Conclusions

Baseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score after GC bridging therapy in RA. Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA.