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Expression of ERAP2 and LST1 is increased before start of therapy in rheumatoid arthritis patients with good clinical response to glucocorticoids
R.D. Fritsch-Stork1, S.C. Silva-Cardoso2, M.J. Groot Koerkamp3, J.C. Broen4, F.F. Lafeber5, J.W. Bijlsma6
- Dept. of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Netherlands; and Ludwig Boltzmann Inst. of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Dept., Hanusch Hospital, Vienna, Austria.
- Laboratory of Translational Immunology, University Medical Center Utrecht, The Netherlands.
- Department of Molecular Cancer Research, University Medical Center Utrecht, The Netherlands.
- Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
- Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, The Netherlands.
- Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, The Netherlands.
CER8868
2016 Vol.34, N°4
PI 0685, PF 0689
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PMID: 27384923 [PubMed]
Received: 15/08/2015
Accepted : 01/02/2016
In Press: 22/06/2016
Published: 14/07/2016
Abstract
OBJECTIVES:
Glucocorticoids (GC) remain a cornerstone of rheumatoid arthritis (RA) therapy, although a third of patients do not respond adequately. In order to find potential predictors for clinical response, the gene expression profile of CD4+T-cells as important players in the pathogenesis of RA was analysed before pulse therapy with 1000 mg methylprednisolone.
METHODS:
Patients were treated with 3x1000 mg methylprednisolone in 5 days; hereafter response was determined by the European League Against Rheumatism (EULAR) response criteria. Before start of treatment, CD4+T-cells (and CD14+monocytes) were separated by MACS sorting. Labelled cRNA from CD4+T-cells from 5 responders and 5 non-responders was hybridised to Agilent 4x44K microarray chips and differentially expressed genes were identified via mixed-model analysis of variance based on permutation-based false discovery rates. Selected genes were validated by quantitative real-time PCR (qPCR).
RESULTS:
Four genes were significantly increased in CD4+T-cells of GC-responders; expression of ERAP2 (endoplasmic reticulum aminopeptidase 2), LST1 (leucocyte-specific transcript 1) and FAM26F (Family With Sequence Similarity 26, Member F) was confirmed by quantitative PCR (qPCR); their expression was inversely correlated with DAS28 at day 5 (LST1 and FAM26F p<0.05; ERAP2: p=0.07). Elevated expression of ERAP2 was also detected by qPCR in CD14+monocytes and after 24 hours in both cell types (all p<0.02).
CONCLUSIONS:
The increased expression of ERAP2, LST1 and FAM26F in GC-responders before therapy warrants further investigation into their role as potential predictors for the response to GC, and in the inflammatory process of RA.
