ArticleProceedings of the National Academy of Sciences of the United States of America2016
Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Host genetic variability and pneumococcal disease: a systematic review and meta-analysis.BMC medical genomics · 2019Pooled it
- Bridging Inflammation and Oncology: The Role and Therapeutic Potential of Macrophage Migration Inhibitory Factor in Lung Cancer.International journal of molecular sciences · 2026Review
- Sphingolipid metabolism-related genes as diagnostic markers in pneumonia-induced sepsis: the AUG model.Scientific reports · 2025Article
- The Role of Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (D-DT/MIF-2) in Infections: A Clinical Perspective.Biomedicines · 2023Review
- Human macrophage migration inhibitory factor potentiates mesenchymal stromal cell efficacy in a clinically relevant model of allergic asthma.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm.Frontiers in immunology · 2022Review
- Review
- Modes of action and diagnostic value of miRNAs in sepsis.Frontiers in immunology · 2022Review
- MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model.The Journal of clinical investigation · 2021Article
- Macrophage-derived cytokines in pneumonia: Linking cellular immunology and genetics.Cytokine & growth factor reviews · 2021Review
- Individual responsiveness of macrophage migration inhibitory factor predicts long-term cognitive impairment after bacterial meningitis.Acta neuropathologica communications · 2021Article
- Trained Immunity Confers Broad-Spectrum Protection Against Bacterial Infections.The Journal of infectious diseases · 2020Article
- The role of host genetics in the immune response to SARS-CoV-2 and COVID-19 susceptibility and severity.Immunological reviews · 2020Review
- Quality Control Measures and Validation in Gene Association Studies: Lessons for Acute Illness.Shock (Augusta, Ga.) · 2020Review
- The Role of MIF-173G/C Gene Polymorphism in the Susceptibility of Autoimmune Diseases.Mediators of inflammation · 2020Article
- Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus.Expert opinion on therapeutic targets · 2019Review
- Macrophage migration inhibitory factor enhances influenza-associated mortality in mice.JCI insight · 2019Article
- The immunobiology of MIF: function, genetics and prospects for precision medicine.Nature reviews. Rheumatology · 2019Review
- Macrophage migration inhibitory factor regulates innate γδ T-cell responsesFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Fulminant arterial vasculitis as an unusual complication of disseminated staphylococcal disease due to the emerging CC1 methicillin-susceptible Staphylococcus aureus clone: a case report.BMC infectious diseases · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 5 countries.
Funding
Abstract
Pneumococcal meningitis is the most frequent and critical type of bacterial meningitis. Because cytokines play an important role in the pathogenesis of bacterial meningitis, we examined whether functional polymorphisms of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) were associated with morbidity and mortality of pneumococcal meningitis. Two functional MIF promoter polymorphisms, a microsatellite (-794 CATT5-8; rs5844572) and a single-nucleotide polymorphism (-173 G/C; rs755622) were genotyped in a prospective, nationwide cohort of 405 patients with pneumococcal meningitis and in 329 controls matched for age, gender, and ethnicity. Carriages of the CATT7 and -173 C high-expression MIF alleles were associated with unfavorable outcome (P= 0.005 and 0.003) and death (P= 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P= 0.02] and carriage of the CATT7 allele (OR 5.12,P= 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P= 0.0002). Streptococcus pneumoniae strongly up-regulated MIF production in whole blood and transcription activity of high-expression MIF promoter Luciferase reporter constructs in THP-1 monocytes. Consistent with these findings, treatment with anti-MIF immunoglogulin G (IgG) antibodies reduced bacterial loads and improved survival in a mouse model of pneumococcal pneumonia and sepsis. The present study provides strong evidence that carriage of high-expression MIF alleles is a genetic marker of morbidity and mortality of pneumococcal meningitis and also suggests a potential role for MIF as a target of immune-modulating adjunctive therapy.
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