B Karakaya1, C H M van Moorsel2, A H M van der Helm-van Mil3, T W J Huizinga4, H J T Ruven5, J J van der Vis6, J C Grutters7. 1. Center of Interstitial Lung Diseases, St. Antonius Hospital, Postbus 2500, 3430 EM Nieuwegein, The Netherlands. Electronic address: B.karakaya@antoniusziekenhuis.nl. 2. Center of Interstitial Lung Diseases, St. Antonius Hospital, Postbus 2500, 3430 EM Nieuwegein, The Netherlands. Electronic address: C.van.moorsel@antoniusziekenhuis.nl. 3. Department of Rheumatology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands. Electronic address: A.H.M.van_der_Helm@lumc.nl. 4. Department of Rheumatology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands. Electronic address: T.W.J.Huizinga@lumc.nl. 5. Department of Clinical Chemistry, St. Antonius Hospital, Postbus 2500, 3430 EM Nieuwegein, The Netherlands. Electronic address: H.ruven@antoniusziekenhuis.nl. 6. Center of Interstitial Lung Diseases, St. Antonius Hospital, Postbus 2500, 3430 EM Nieuwegein, The Netherlands. Electronic address: A.vandervis@antoniusziekenhuis.nl. 7. 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.
Abstract
INTRODUCTION: 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.
INTRODUCTION: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 sarcoidosispatients 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: Atiyeh M Abdallah; Abdulhadi H Al-Mazroea; Waleed N Al-Harbi; Nabeeh A Al-Harbi; Amr E Eldardear; Yousef Almohammadi; Khalid M Al-Harbi Journal: Front Immunol Date: 2016-03-14 Impact factor: 7.561