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Ann Rheum Dis 2007;66:1525-1530 doi:10.1136/ard.2006.064394
  • Extended report

Macrophage migration inhibitory factor polymorphisms do not predict therapeutic response to glucocorticoids or to tumour necrosis factor α-neutralising treatments in rheumatoid arthritis

  1. Timothy R D J Radstake1,
  2. Jaap Fransen1,
  3. Erik J M Toonen2,
  4. Marieke J H Coenen2,
  5. Agnes E Eijsbouts3,
  6. Rachelle Donn4,
  7. Frank H J van den Hoogen1,3,
  8. Piet L C M van Riel1
  1. 1
    Departments of Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Centre Nijmegen, The Netherlands
  2. 2
    Departments of Human Genetics,  = Radboud University Nijmegen Medical Centre Nijmegen, The Netherlands
  3. 3
    St. Maartenskliniek, Nijmegen, The Netherlands
  4. 4
    University of Manchester, Manchester, UK
  1. T R D J Radstake, MD, PhD, Department of Rheumatology, Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, PO 6525 GA, Nijmegen, The Netherlands; t.radstake{at}reuma.umcn.nl
  • Accepted 14 April 2007
  • Published Online First 24 April 2007

Abstract

Background: Macrophage migration inhibitory factor (MIF) is an inflammatory mediator associated with RA severity. In various diseases, MIF polymorphisms are associated with clinical response glucocorticoid (GC) treatment. It is unclear whether MIF polymorphisms determine GC response in rheumatoid arthritis (RA) and to other RA treatments. Therefore, the question of whether two functional variants in MIF are associated with the response to tumour necrosis factor (TNF)α-neutralising and GC treatments in RA was investigated.

Methods: Data from two cohorts of an RA registry were used. For patients who started with TNFα-neutralising (infliximab) or GC treatment, courses with a duration of at least 3 months were included and response to TNFα blockers or GC was calculated according to the European League Against Rheumatism response criteria. MIF −173G→C genotyping was achieved using an assay-on-demand allelic discrimination assay, and alleles of the CATT repeat element were identified using a fluorescently labelled PCR primer and capillary electrophoresis. Logistic-regression modelling was used for the statistical analysis.

Results: In total, 192 courses of oral prednisone or methylprednisolone injections in 98 patients with RA and 90 patients with RA who were on TNFα-neutralising treatments were documented. In all, 27% of the patients with RA were found to be heterozygous for seven CATT repeats (CATT7) and 31% were heterozygous for −173C. Respectively, 4% and 6% of the patients with RA were homozygous for the MIF CATT7 repeat or the MIF −173C allele. Carrier status and homozygosity for CATT7 repeat and the MIF −173C allele were not associated with response to GC (odds ratios (ORs) close to 1) or to TNFα-neutralising treatment (ORs close to 2).

Conclusion: The MIF-CATT7 repeat and the MIF−173G→C functional variant are not strongly associated with a decreased clinical response to TNFα-neutralising or GC treatment in RA.

Footnotes

  • The first two authors contributed equally to this work.

  • Abbreviations:
    DAS
    Disease Activity Score
    DMARD
    disease-modifying antirheumatic drug
    ESR
    erythrocyte sedimentation rate
    EULAR
    European League Against Rheumatism
    GC
    glucocorticoid
    IL
    interleukin
    JIA
    juvenile idiopathic arthritis
    MIF
    migration inhibitory factor
    RA
    rheumatoid arthritis
    RUNMC
    Radboud University Nijmegen Medical Centre
    SF
    synovial fluid
    SLE
    systemic lupus erythematosus
    TLR
    Toll-like receptor
    TNF
    tumour necrosis factor

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