Macrophage migration inhibitory factor -173 polymorphism and risk of coronary alterations in children with Kawasaki disease
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Published on: April 3, 2017
G Simonini1, E Corinaldesi, C Massai
1Department of Paediatrics, Rheumatology Unit, A. Meyer Children's Hospital, Florence, Italy. gabriele.simonini@unifi.it
Insights
The macrophage migration inhibitory factor (MIF) -173*C polymorphism is linked to an increased risk of coronary artery abnormalities (CAA) in children with Kawasaki disease (KD). This genetic factor also correlates with a higher likelihood of non-response to initial intravenous immunoglobulin (IVIG) treatment.
Area of Science:
- Genetics
- Immunology
- Pediatrics
Background:
- Kawasaki disease (KD) is an acute febrile illness affecting young children, primarily causing inflammation of medium-sized arteries.
- Coronary artery abnormalities (CAA) are the most serious complication of KD, leading to long-term cardiovascular risks.
- Genetic predisposition is suspected to play a role in KD susceptibility and severity, but specific genetic markers are still under investigation.
Purpose of the Study:
- To investigate the association between the macrophage migration inhibitory factor (MIF) -173 G/C gene polymorphism and the susceptibility to, and severity of, Kawasaki disease (KD) in Italian children.
- To determine if this MIF polymorphism influences the development of coronary artery abnormalities (CAA) or response to intravenous immunoglobulin (IVIG) treatment in KD patients.
Main Methods:
- Genotyping for the MIF -173 G/C polymorphism was performed using PCR and restriction fragment length polymorphism (RFLP) analysis.
- The study included 69 Italian children diagnosed with KD and 60 healthy Caucasian children as controls.
- Clinical data, including the development of CAA and response to IVIG, were collected and analyzed in relation to the MIF genotype.
Main Results:
- No significant difference in MIF genotype frequencies was observed between KD patients and healthy controls.
- KD patients carrying the MIF -173*C allele showed a significantly higher frequency of developing coronary artery abnormalities (CAA) compared to those without the allele (77.8% vs. 26.7%).
- Children with the MIF -173*C allele were also more likely to be non-responders to initial IVIG treatment (75% vs. 28%) and had an increased risk of coronary involvement in regression analysis.
Conclusions:
- The study suggests a potential relationship between the MIF -173*C polymorphism and an increased risk of developing coronary artery abnormalities (CAA) in Kawasaki disease (KD) patients.
- Carriage of the MIF -173*C allele may be a predictive factor for poor response to IVIG and increased risk of coronary complications in KD.
- Further research is warranted to elucidate the role of MIF in KD pathogenesis and its implications for treatment strategies.
Objective:
To investigate the possible relationship between MIF -173 polymorphism and susceptibility to, and severity of, Kawasaki disease (KD) in a cohort of Italian patients.
Methods:
Sixty-nine patients (43 F, 26 M, median age 29 months, range 3-135 months) with KD and 60 sex-matched healthy caucasian children were genotyped for MIF-173. Typing of the MIF gene -173 G/C was performed by PCR and restriction fragment length polymorphism.
Results:
Eight out of 69 (12%) KD children were non-responders: 7 required an additional IVIG infusion, while 1 received 2 IVIG infusions and then steroid administration. 9/69 (13%) KD children developed coronary artery abnormalities (CAA) during the second to fourth week of disease, and 4 of them required an additional IVIG infusion. MIF genotyping did not show significant differences between patients and controls. KD patients carrying a MIF -173*C allele developed CAA more frequently than those without MIF- (7/9 77.8% vs. 16/60 26.7%, OR 9.6, 95% CI 1.80-21.2, p<0.005). Non-responders to a single IVIG infusion carried the MIF -173*C allele more frequently than responders (6/8 = 75% vs. 17/61 = 28%, OR 5.1, 95% CI 1.42-22.31 p<0.014). In multiple regression analysis, KD patients carrying a MIF -173*C allele were found to have an increased risk of coronary involvement (OR 7.7, 95% CI 1.36-16.1, p=0.021).
Conclusions:
We showed that children carrying the MIF polymorphism -173*C had a higher percentage of CAA. A potential relationship between a MIF polymorphism and risk of CAA in KD might be considered.