title: Macrophage migration inhibitory factor polymorphisms do not predict therapeutic response to glucocorticoids or to tumour necrosis factor alpha-neutralising treatments in rheumatoid arthritis.
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)alpha-neutralising and GC treatments in RA was investigated.
  
  
  METHODS
  Data from two cohorts of an RA registry were used. For patients who started with TNFalpha-neutralising (infliximab) or GC treatment, courses with a duration of at least 3 months were included and response to TNFalpha 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 TNFalpha-neutralising treatments were documented. In all, 27% of the patients with RA were found to be heterozygous for seven CATT repeats (CATT(7)) and 31% were heterozygous for -173C. Respectively, 4% and 6% of the patients with RA were homozygous for the MIF CATT(7) repeat or the MIF -173C allele. Carrier status and homozygosity for CATT(7 )repeat and the MIF -173C allele were not associated with response to GC (odds ratios (ORs) close to 1) or to TNFalpha-neutralising treatment (ORs close to 2).
  
  
  CONCLUSIONS
  The MIF-CATT(7) repeat and the MIF-173G-->C functional variant are not strongly associated with a decreased clinical response to TNFalpha-neutralising or GC treatment in RA.
authors: Department of Rheumatology, Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, PO 6525 GA, Nijmegen, The Netherlands. t.radstake@reuma.umcn.nl
authors: Timothy R D J
authors: TR
authors: Radstake
authors: Jaap
authors: J
authors: Fransen
authors: Erik J M
authors: EJ
authors: Toonen
authors: Marieke J H
authors: MJ
authors: Coenen
authors: Agnes E
authors: AE
authors: Eijsbouts
authors: Rachelle
authors: R
authors: Donn
authors: Frank H J
authors: FH
authors: van den Hoogen
authors: Piet L C M
authors: PL
authors: van Riel
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D012042:Registries; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D005938:Glucocorticoids; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab