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

Rogier A M Quax; Jan W Koper; Pascal H P de Jong; Ramona van Heerebeek; Angelique E Weel; Anne M Huisman; Derkjen van Zeben; Frank H de Jong; Steven W J Lamberts; Johanna M W Hazes; Richard A Feelders

doi:10.1186/ar4029

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

Rogier A M Quax^*, Jan W Koper, Pascal H P de Jong, Ramona van Heerebeek, Angelique E Weel, Anne M Huisman, Derkjen van Zeben, Frank H de Jong, Steven W J Lamberts, Johanna M W Hazes, Richard A Feelders

^*Corresponding author for this work

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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).

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.

Original language	English
Article number	R195
Journal	Arthritis Research & Therapy
Volume	14
Issue number	4
DOIs	https://doi.org/10.1186/ar4029
Publication status	Published - 24 Aug 2012

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EMC MM-01-39-01
EMC MM-01-39-04
EMC MUSC-01-31-01

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Repub_62501_O-A.pdfFinal published version, 1.7 MBLicence: CC BY

http://hdl.handle.net/1765/62501

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Quax, R. A. M., Koper, J. W., de Jong, P. H. P., van Heerebeek, R., Weel, A. E., Huisman, A. M., van Zeben, D., de Jong, F. H., Lamberts, S. W. J., Hazes, J. M. W., & Feelders, R. A. (2012). In vitro glucocorticoid sensitivity is associated with clinical glucocorticoid therapy outcome in rheumatoid arthritis. Arthritis Research & Therapy, 14(4), Article R195. https://doi.org/10.1186/ar4029

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title = "In vitro glucocorticoid sensitivity is associated with clinical glucocorticoid therapy outcome in rheumatoid arthritis",

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).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.",

author = "Quax, {Rogier A M} and Koper, {Jan W} and {de Jong}, {Pascal H P} and {van Heerebeek}, Ramona and Weel, {Angelique E} and Huisman, {Anne M} and {van Zeben}, Derkjen and {de Jong}, {Frank H} and Lamberts, {Steven W J} and Hazes, {Johanna M W} and Feelders, {Richard A}",

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doi = "10.1186/ar4029",

language = "English",

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journal = "Arthritis Research & Therapy",

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T1 - In vitro glucocorticoid sensitivity is associated with clinical glucocorticoid therapy outcome in rheumatoid arthritis

AU - Quax, Rogier A M

AU - Koper, Jan W

AU - de Jong, Pascal H P

AU - van Heerebeek, Ramona

AU - Weel, Angelique E

AU - Huisman, Anne M

AU - van Zeben, Derkjen

AU - de Jong, Frank H

AU - Lamberts, Steven W J

AU - Hazes, Johanna M W

AU - Feelders, Richard A

PY - 2012/8/24

Y1 - 2012/8/24

N2 - 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).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.

AB - 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).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.

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DO - 10.1186/ar4029

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JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

IS - 4

M1 - R195

ER -

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

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