title: Expression of ERAP2 and LST1 is increased before start of therapy in rheumatoid arthritis patients with good clinical response to glucocorticoids.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Ruth D E
authors.initials: RD
authors.lastname: Fritsch-Stork
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, The Netherlands.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Silva-Cardoso
authors.affiliation: Department of Molecular Cancer Research, University Medical Center Utrecht, The Netherlands.
authors.forename: Marjan J A
authors.initials: MJ
authors.lastname: Groot Koerkamp
authors.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Jasper C A
authors.initials: JC
authors.lastname: Broen
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, The Netherlands.
authors.forename: Floris F P
authors.initials: FF
authors.lastname: Lafeber
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, The Netherlands.
authors.forename: Johannes W J Bijlsma
authors.initials: JW
authors.lastname: Bijlsma
mesh_terms: D000328:Adult; D000626:Aminopeptidases / Q000097:blood / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics*; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018579:Patient Selection; D010865:Pilot Projects; D011237:Predictive Value of Tests; D020551:Pulse Therapy, Drug; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: C000599332:CALHM6 protein, human; D005819:Genetic Markers; D005938:Glucocorticoids; D047908:Intracellular Signaling Peptides and Proteins; C093604:LST1 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000626:Aminopeptidases; C503944:ERAP2 protein, human; D008775:Methylprednisolone