Related Experiment Video
Updated: Aug 15, 2026
Cystic Fibrosis Aggregate Biofilm Model to Study Infection-relevant Gene Expression
Published on: April 18, 2025
Cystic fibrosis, disease severity, and a macrophage migration inhibitory factor polymorphism
Barry J Plant1, Charles G Gallagher, Richard Bucala
1F.R.C.P.I., Department of Medicine and Therapeutics, The Education Research Centre, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. seamas.donnelly@ucd.ie
Rationale:
Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator. It contributes toward an exaggerated gram-negative inflammatory response via its ability to induce Toll-like receptor-4 expression. Studies have shown that MIF knockout mice have less aggressive Pseudomonas infection (compared with wild-type).
Objectives:
To assess whether a novel functional MIF polymorphism was associated with clinical prognosis in a patient cohort with chronic gram-negative infection, namely cystic fibrosis (CF).
Methods:
Collected genomic DNA was analyzed via polymerase chain reaction amplification for the polymorphic region for the CATT repeat polymorphism. Individuals may have a 5-, 6-, 7-, or 8-CATT tetranucleotide repeat unit on each allele. The 5-CATT repeat allele exhibits the lowest MIF promoter activity.
Measurements And Main Results:
Patients with stable CF (n = 167) and a matched control group (n = 166) were enrolled. In patients with CF, the MIF5(+) group had a decreased incidence of Pseudomonas aeruginosa colonization (odds ratio, 0.25; 95% confidence interval, 0.09-0.65; p = 0.004) and a significant reduction in the risk of pancreatic insufficiency (odds ratio, 0.27; 95% confidence interval, 0.07-1.0; p = 0.05). A trend toward milder disease activity in the MIF5(+) group was seen with all other parameters.
Conclusions:
The results support the concept of a regulatory role for MIF in CF.
Insights
A specific gene variant in macrophage migration inhibitory factor (MIF) is linked to better outcomes in cystic fibrosis (CF) patients. This MIF polymorphism reduces Pseudomonas aeruginosa colonization and pancreatic insufficiency risk in individuals with CF.
Area of Science:
- Immunology
- Genetics
- Pulmonology
Background:
- Macrophage migration inhibitory factor (MIF) is a key mediator of inflammation, exacerbating gram-negative infections by upregulating Toll-like receptor-4.
- MIF knockout mice exhibit reduced susceptibility to Pseudomonas infections, suggesting a role in host defense.
Purpose of the Study:
- To investigate the association between a novel functional MIF polymorphism and clinical prognosis in cystic fibrosis (CF) patients with chronic gram-negative infections.
- To determine if the CATT repeat polymorphism in the MIF gene influences disease severity and complications in CF.
Main Methods:
- Genomic DNA from 167 CF patients and 166 controls was analyzed for the MIF CATT repeat polymorphism using polymerase chain reaction.
- Alleles were classified by the number of CATT tetranucleotide repeat units (5, 6, 7, or 8), with the 5-repeat allele showing the lowest MIF promoter activity.
Main Results:
- Patients with the MIF 5-repeat allele (MIF5(+)) had significantly lower odds of Pseudomonas aeruginosa colonization (OR, 0.25; P = 0.004).
- The MIF5(+) genotype was associated with a reduced risk of pancreatic insufficiency in CF patients (OR, 0.27; P = 0.05).
- A trend towards milder disease activity was observed in the MIF5(+) group across other clinical parameters.
Conclusions:
- The findings support a regulatory role for macrophage migration inhibitory factor (MIF) in the pathogenesis and clinical course of cystic fibrosis.
- The MIF CATT repeat polymorphism may serve as a predictive biomarker for disease progression and complications in CF patients.
