title: Macrophage migration inhibitory factor (MIF) -173 polymorphism is associated with clinical erythema nodosum in Löfgren's syndrome.
abstract: BACKGROUND
  Macrophage migration inhibitory factor (MIF) has been shown to be a key regulator in innate and adaptive immune responses. A single nucleotide polymorphism in the 5' region of the MIF gene, MIF -173∗G/C, is associated with increased MIF protein production, in vivo and in vitro. Associations have been shown between the minor MIF -173C allele and sarcoidosis patients with erythema nodosum (EN). Löfgren's syndrome is an acute and usually self-remitting phenotype of sarcoidosis. It is defined as having an acute onset with bilateral hilar lymphadenopathy (BHL), fever, erythema nodosum (EN) and/or arthritis. The aim of this study was to investigate whether MIF -173G/C associates with the susceptibility to and the clinical manifestations, i.e. arthritis or EN, of Löfgren's syndrome. A total of 171 patients with Löfgren's syndrome and 313 controls were genotyped for a single nucleotide polymorphism at position -173 of the MIF gene (SNP rs755622), using a PCR and a restriction enzyme technique.
  
  
  RESULTS
  There were no significant differences found in the MIF -173C allele frequencies between patients with Löfgren's syndrome and controls. In patients with Löfgren's syndrome with only EN, a significantly increased frequency of the C minor allele was observed compared to patients with arthritis only (p=0.0095; OR 3.08, CI: 1.28-7.39). Patients with only EN compared to patients with EN and arthritis showed a significantly increased frequency of the minor C allele (p=0.044; OR 1.97, CI: 1.01-3.85). But patients with only arthritis compared to patients with EN and arthritis did not show a significant difference in C allele frequency (p=0.270; OR 0.64, CI: 0.29-1.42).
  
  
  CONCLUSIONS
  The MIF -173C allele is associated with erythema nodosum in Löfgren's syndrome, but not with susceptibility to sarcoidosis. This indicates a role for MIF after antigen presenting to the T cell has taken place and the sarcoid inflammatory response has begun.
authors.affiliation: Center of Interstitial Lung Diseases, St. Antonius Hospital, Postbus 2500, 3430 EM Nieuwegein, The Netherlands. Electronic address: B.karakaya@antoniusziekenhuis.nl.
authors.forename: B
authors.initials: B
authors.lastname: Karakaya
authors.affiliation: Center of Interstitial Lung Diseases, St. Antonius Hospital, Postbus 2500, 3430 EM Nieuwegein, The Netherlands. Electronic address: C.van.moorsel@antoniusziekenhuis.nl.
authors.forename: C H M
authors.initials: CH
authors.lastname: van Moorsel
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands. Electronic address: A.H.M.van_der_Helm@lumc.nl.
authors.forename: A H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands. Electronic address: T.W.J.Huizinga@lumc.nl.
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Clinical Chemistry, St. Antonius Hospital, Postbus 2500, 3430 EM Nieuwegein, The Netherlands. Electronic address: H.ruven@antoniusziekenhuis.nl.
authors.forename: H J T
authors.initials: HJ
authors.lastname: Ruven
authors.affiliation: Center of Interstitial Lung Diseases, St. Antonius Hospital, Postbus 2500, 3430 EM Nieuwegein, The Netherlands. Electronic address: A.vandervis@antoniusziekenhuis.nl.
authors.forename: J J
authors.initials: JJ
authors.lastname: van der Vis
authors.affiliation: Center of Interstitial Lung Diseases, St. Antonius Hospital, Postbus 2500, 3430 EM Nieuwegein, The Netherlands; Division of Heart & Lungs, University Medical Center Utrecht, Postbus 85500, 3508 GA Utrecht, The Netherlands. Electronic address: J.grutters@antoniusziekenhuis.nl.
authors.forename: J C
authors.initials: JC
authors.lastname: Grutters
mesh_terms: D000328:Adult; D001168:Arthritis; D016022:Case-Control Studies; D004893:Erythema Nodosum / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012507:Sarcoidosis / Q000150:complications / Q000235:genetics*; D013577:Syndrome
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: Erythema nodosum; Löfgren’s syndrome; Macrophage migration inhibitory factor (MIF); Sarcoidosis; Single nucleotide polymorphism (SNP)