Cystic fibrosis, disease severity, and a macrophage migration inhibitory factor polymorphism.
BACKGROUND
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).


OBJECTIVE
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.


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.
Plant
Barry J
BJ
F.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
Gallagher
Charles G
CG
Bucala
Richard
R
Baugh
John A
JA
Chappell
Sally
S
Morgan
Linda
L
O'Connor
Clare M
CM
Morgan
Kevin
K
Donnelly
Seamas C
SC
D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index
C505032:CFTR protein, human; D008263:Macrophage Migration-Inhibitory Factors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA