C-C chemokine receptor 5 (CCR5) and polymorphisms in CCR5 gene are associated with sarcoidosis and Lofgren's syndrome. Lofgren's syndrome is an acute and usually self-remitting phenotype of... Show moreC-C chemokine receptor 5 (CCR5) and polymorphisms in CCR5 gene are associated with sarcoidosis and Lofgren's syndrome. Lofgren's syndrome is an acute and usually self-remitting phenotype of sarcoidosis. We investigated whether the single nucleotide polymorphism (SNP) rs1799987 is associated with susceptibility for Lofgren's syndrome and has an effect on CCR5 expression on monocytes and function of CCR5. A total of 106 patients with Lofgren's syndrome and 257 controls were genotyped for rs1799987. Expression of CCR5 on monocytes was measured by flowcytometry. We evaluated calcium influx kinetics following stimulation upon N-formylmethionyl-leucyl-phenylalanine (fMLP) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) on monocytes by measuring the median fluorescence intensity (MFI). The frequency of the G allele of rs1799987 was significantly higher in Lofgren's syndrome than in healthy controls (p = 0.0015, confidence interval (CI) 1.22-2.32, odds ratio (OR) 1.680). Patients with a GG genotype showed higher CCR5 expression on monocytes than patients with the AA genotype (p = 0.026). A significantly (p = 0.027) lower count of patients with the GG genotype showed a calcium influx reaction to simulation upon MIP-1 alpha, compared with patients with the AA genotype. The rs1799987 G allele in CCR5 gene is associated with susceptibility to Lofgren's syndrome and with quantitative and qualitative changes in CCR5, potentially effecting the inflammatory response. Show less
INTRODUCTION\nMacrophage 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... Show moreINTRODUCTION\nMacrophage 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.\nRESULTS\nThere 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).\nCONCLUSIONS\nThe 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. Show less
Karakaya, B.; Vreeburg, M.D.; Megens, H.J.; van't Slot, R.; Bevova, M.; Ruven, H.J.T.; ... ; Moorsel, C.H.M. van 2013
