| Dual effect of the macrophage migration inhibitory factor gene on the development and severity of human systemic lupus erythematosus. | |
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MedLine Citation:
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PMID: 22127710 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To study the effect of the innate cytokine macrophage migration inhibitory factor (MIF) on the susceptibility and severity of systemic lupus erythematosus (SLE) in a multinational population of 1,369 Caucasian and African American patients. METHODS: Two functional polymorphisms in the MIF gene, a -794 CATT(5-8) microsatellite repeat (rs5844572) and a -173 G/C single-nucleotide polymorphism (rs755622), were assessed for association with SLE in 3,195 patients and healthy controls. We also measured MIF plasma levels in relation to genotypes and clinical phenotypes, and assessed Toll-like receptor 7 (TLR-7)-stimulated MIF production in vitro. RESULTS: Both Caucasians and African Americans with the high-expression MIF haplotype -794 CATT(7)/-173*C had a lower incidence of SLE (in Caucasians, odds ratio [OR] 0.63, 95% confidence interval [95% CI] 0.53-0.89, P = 0.001; in African Americans, OR 0.46, 95% CI 0.23-0.95, P = 0.012). In contrast, among patients with established SLE, reduced frequencies of low-expression MIF genotypes (-794 CATT(5)) were observed in those with nephritis, those with serositis, and those with central nervous system (CNS) involvement when compared to patients without end-organ involvement (P = 0.023, P = 0.005, and P = 0.04, respectively). Plasma MIF levels and TLR-7-stimulated MIF production in vitro reflected the underlying MIF genotype of the studied groups. CONCLUSION: These findings suggest that MIF, which has both proinflammatory properties and macrophage and B cell survival functions, exerts a dual influence on the immunopathogenesis of SLE. High-expression MIF genotypes are associated with a reduced susceptibility to SLE and may contribute to an enhanced clearance of infectious pathogens. Once SLE develops, however, low-expression MIF genotypes may protect from ensuing inflammatory end-organ damage. |
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Authors:
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Antoine Sreih; Rana Ezzeddine; Lin Leng; Avery LaChance; Geraldine Yu; Yuka Mizue; Lakshman Subrahmanyan; Bernardo A Pons-Estel; Anna-Karin Abelson; Iva Gunnarsson; Elisabet Svenungsson; Joshua Cavett; Stuart Glenn; Lin Zhang; Ruth Montgomery; Andras Perl; Jane Salmon; Marta E Alarcón-Riquelme; John B Harley; Richard Bucala |
Publication Detail:
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Type: Comparative Study; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Arthritis and rheumatism Volume: 63 ISSN: 1529-0131 ISO Abbreviation: Arthritis Rheum. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-11-30 Completed Date: 2012-01-27 Revised Date: 2012-04-25 |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
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Languages: eng Pagination: 3942-51 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 by the American College of Rheumatology. |
Affiliation:
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Yale University School of Medicine, New Haven, Connecticut 06520, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult African Americans / ethnology Case-Control Studies Cross-Sectional Studies European Continental Ancestry Group / ethnology Female Genetic Predisposition to Disease / genetics* Genotype Humans Lupus Erythematosus, Systemic / blood, ethnology, genetics* Macrophage Migration-Inhibitory Factors / blood, genetics* Male Middle Aged Phenotype Polymorphism, Single Nucleotide / genetics* Severity of Illness Index* Tumor Necrosis Factor-alpha / blood |
| Grant Support | |
ID/Acronym/Agency:
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AR-049610/AR/NIAMS NIH HHS; AR-050498/AR/NIAMS NIH HHS; N01-AI-50031/AI/NIAID NIH HHS; R01 AR049610/AR/NIAMS NIH HHS; R01 AR049610-08/AR/NIAMS NIH HHS; R01 AR049610-11/AR/NIAMS NIH HHS; R01 AR050498-08/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Macrophage Migration-Inhibitory Factors; 0/Tumor Necrosis Factor-alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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