Macrophage migration inhibitory factor (MIF) -173 polymorphism is associated with clinical erythema nodosum in Löfgren's syndrome

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.