Macrophage migration inhibitory factor: An emerging therapeutic target in rheumatoid arthritis

Morand, Eric Francis; Bucala, Richard; Leech, Michelle

doi:10.1002/art.10728

Cited by 64 publications

(54 citation statements)

References 77 publications

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“…Baugh et al demonstrated that presence of specific alleles of the MIF CATT tetranucleotide repeat correlate with the severity of RA (5). In contrast with this finding, Barton and colleagues found that the MIF Ϫ173C allele and the MIF CATT 7 repeat were associated with susceptibility to inflammatory arthritis, but they were unable to find a correlation with disease severity (14). Susceptibility to juvenile idiopathic arthritis was found to be associated with both functional promotor polymorphisms in the MIF gene (6,15).…”

mentioning

confidence: 98%

“…The identification of the single-nucleotide polymorphism at position Ϫ173 (MIF Ϫ173GϾC) and a CATT [5][6][7][8] tetranucleotide repeat element starting at position Ϫ794 in the promoter region of the MIF gene has sparked research into the role of these variants in inflammatory conditions. Baugh et al demonstrated that presence of specific alleles of the MIF CATT tetranucleotide repeat correlate with the severity of RA (5).…”

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confidence: 99%

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Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor

Radstake

Sweep

Welsing

et al. 2005

Arthritis & Rheumatism

190

184

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Objective. To study whether genetic variants of macrophage migration inhibitory factor (MIF), the MIF ؊173G>C and CATT 5-8 alleles, are associated with disease severity and levels of circulating MIF in patients with rheumatoid arthritis (RA).Methods. Genotyping was performed in patients with early RA and in healthy controls. Demographic data, disease activity, and outcome measurements were compared between patients with and without the MIF variants. MIF ؊173G>C and CATT 5-8 polymorphisms were genotyped, and a newly developed enzyme-linked immunosorbent assay for human MIF was used. Allele and genotype distributions of the MIF ؊173G>C and CATT 5-8 polymorphisms were compared between patients and controls by chi-square test. Multiple regression analysis was performed to assess the independence of the MIF functional genetic variants as risk factors for radiologic joint damage.Results. Genotyping of the ؊173G>C and CATT 5-8 polymorphisms of MIF in RA patients and healthy individuals (n ‫؍‬ 277 each) revealed similar frequencies of genotypes and haplotypes in both groups. No significant differences in demographic or clinical features were observed between RA patients carrying the MIF ؊173C allele or the MIF CATT 7 allele or both and noncarrier RA patients. Radiologic joint damage was significantly higher in patients carrying risk alleles of the MIF ؊173G>C or the MIF CATT 5-8 functional variants. No synergistic effects between both genetic variants were observed. Multivariate regression analysis revealed that presence of the MIF ؊173C/C and MIF CATT 7/7 genotypes and having 1 MIF ؊173C allele were independent prognostic variables. Carriership of the MIF ؊173C allele (P ‫؍‬ 0.002) or MIF CATT 7 allele (P ‫؍‬ 0.004) was associated with significantly higher circulating MIF levels compared with those in subjects having none of the risk-conferring alleles, and greater circulating MIF levels correlated with more severe radiologic joint damage (r ‫؍‬ 0.64, P ‫؍‬ 0.001).Conclusion. The MIF polymorphisms are not associated with RA susceptibility but are associated with high levels of radiologic joint damage. High circulating MIF levels were shown to correlate strongly with radiologic joint damage, suggesting that MIF expression is genetically determined and can be used as a novel prognostic tool in RA.

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confidence: 98%

mentioning

confidence: 99%

Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor

Radstake

Sweep

Welsing

et al. 2005

Arthritis & Rheumatism

190

184

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“…Macrophages are also now identified as an important source of MIF and are known to express MIF both constitutively and upon stimulation [15]. Macrophage migration inhibitory factor is considered to act by both paracrine and autocrine stimulatory pathways to augment the activation of these cells [15]. As reported previously, MIF is essential for T cell activation and possibly contributes to maintaining Th1/Th2 imbalance [1].…”

Section: Introductionmentioning

confidence: 93%

“…Investigations in the 1990s aimed at identifying novel systemic mediators that could regulate host inflammatory responses led to the identification of murine MIF as a product secreted by the anterior pituitary gland [2]. Upon stimulation, T cells release MIF, and MIF activity was first described as a product of cognate T cell supernatants [15]. Macrophages are also now identified as an important source of MIF and are known to express MIF both constitutively and upon stimulation [15].…”

Section: Introductionmentioning

confidence: 99%

“…Upon stimulation, T cells release MIF, and MIF activity was first described as a product of cognate T cell supernatants [15]. Macrophages are also now identified as an important source of MIF and are known to express MIF both constitutively and upon stimulation [15]. Macrophage migration inhibitory factor is considered to act by both paracrine and autocrine stimulatory pathways to augment the activation of these cells [15].…”

Section: Introductionmentioning

confidence: 99%

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Increase in macrophage migration inhibitory factor levels in lacrimal fluid of patients with severe atopic dermatitis

Shimizu

Honda

Abe

et al. 2005

Graefe's Arch Clin Exp Ophthalmo

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A functional promoter haplotype of macrophage migration inhibitory factor is linked and associated with juvenile idiopathic arthritis

Donn¹,

Alourfi²,

Zeggini³

et al. 2004

Arthritis & Rheumatism

115

109

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Objective. To establish linkage and replicate the association of macrophage migration inhibitory factor (MIF) with juvenile idiopathic arthritis (JIA).Methods. Three hundred twenty-one Caucasian simplex families from the UK were genotyped for polymorphisms of MIF using SNaPshot ddNTP primer extension, or by a fluorescently labeled primer method, and capillary gel electrophoresis. The functional significance of the promoter polymorphisms was studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines.Results. MIF was linked and associated with JIA (P ‫؍‬ 0.0016). Specifically, a 2-point promoter haplotype, CATT 7 -MIF-173*C, was found to be transmitted in excess (38 transmitted: 21 not transmitted) in the JIA patients. Conditional extended transmission disequilibrium test and pairwise extended transmission disequilibrium test predicted functional interaction between the 2 polymorphic positions. The interaction of the CATT repeat with MIF-173*G/C was found to be specific to the cell type.Conclusion. Replication of an association and linkage of MIF with JIA has been established. Functional interaction between the polymorphic positions on the linked haplotype has also been shown. The molecular mechanism of this interaction is currently being investigated.

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Macrophage migration inhibitory factor: An emerging therapeutic target in rheumatoid arthritis

Cited by 64 publications

References 77 publications

Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor

Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor

Increase in macrophage migration inhibitory factor levels in lacrimal fluid of patients with severe atopic dermatitis

A functional promoter haplotype of macrophage migration inhibitory factor is linked and associated with juvenile idiopathic arthritis

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