Expression of ERAP2 and LST1 is increased before start of therapy in rheumatoid arthritis patients with good clinical response to glucocorticoids

Clin Exp Rheumatol. 2016 Jul-Aug;34(4):685-9. Epub 2016 Jun 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aminopeptidases / blood
  • Aminopeptidases / genetics*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • CD4-Positive T-Lymphocytes / metabolism*
  • Female
  • Gene Expression Profiling / methods
  • Genetic Markers
  • Glucocorticoids / administration & dosage*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Proteins / blood
  • Membrane Proteins / genetics*
  • Methylprednisolone / administration & dosage*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Patient Selection
  • Pilot Projects
  • Predictive Value of Tests
  • Pulse Therapy, Drug
  • Real-Time Polymerase Chain Reaction
  • Treatment Outcome
  • Up-Regulation

Substances

  • CALHM6 protein, human
  • Genetic Markers
  • Glucocorticoids
  • Intracellular Signaling Peptides and Proteins
  • LST1 protein, human
  • Membrane Glycoproteins
  • Membrane Proteins
  • Aminopeptidases
  • ERAP2 protein, human
  • Methylprednisolone