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Published on: August 7, 2017
Infants with Down syndrome and congenital heart disease have altered peri-operative immune responses
Lyudmyla Zakharchenko1,2, Afif El-Khuffash2,3,4,5, Tim Hurley5
1Paediatric Cardiology, Children's Health Ireland at Crumlin & Tallaght, Dublin, Ireland.
Insights
Infants with Down syndrome and congenital heart disease exhibit altered immune responses, with lower cytokine levels and higher EPO/GM-CSF. This immune dysregulation may impact clinical outcomes and inform tailored therapies.
Area of Science:
- Immunology
- Pediatric Cardiology
- Genetics
Background:
- Infants with Down syndrome (DS) possess an altered immune response.
- Congenital heart disease (CHD) is common in infants with DS.
- Understanding peri-operative immune changes in DS/CHD is crucial.
Purpose of the Study:
- To characterize the peri-operative inflammatory response in infants with DS and CHD.
- To compare immune profiles of DS/CHD infants to CHD-only and healthy infants.
- To explore the potential link between immune alterations and clinical outcomes.
Main Methods:
- Prospective recruitment of three infant groups: DS/CHD, CHD only, and healthy controls.
- Serial serum cytokine evaluation using multiplex ELISA.
- Measurement of key inflammatory markers including TNF-α, ILs, VEGF, GM-CSF, and EPO.
Main Results:
- Infants with DS/CHD showed significantly lower concentrations of several cytokines (e.g., IL-10, IL-6, IL-8, IL-1β, VEGF) pre- and post-operatively compared to controls.
- Erythropoietin (EPO) and granulocyte macrophage colony-stimulating factor (GM-CSF) were significantly higher in the DS/CHD group.
- These immune alterations were observed in both pre- and post-operative periods.
Conclusions:
- Children with DS/CHD exhibit distinct peri-operative immune alterations, including reduced cytokine levels and increased EPO/GM-CSF.
- These immune changes may contribute to adverse clinical outcomes such as sepsis and autoimmunity.
- Assessing the peri-operative inflammatory state can aid in developing predictive models and tailored immunomodulatory therapies.
Background:
Infants with Down syndrome (DS) have an altered immune response. We aimed to characterise the inflammatory response in infants with DS and congenital heart disease (CHD) peri-operatively in comparison to infants with CHD and a normal chromosomal complement, and to healthy infants pre-operatively.
Methods:
Infants with DS/CHD, infants without DS but with CHD (CHD only) and healthy infants were prospectively recruited and serial serum cytokines evaluated peri-operatively using multiplex ELISA: tumour necrosis factor (TNF)-α and TNF-β; interferon (IFN)-γ, interleukin (IL)-1α, IL-2, IL-6, IL-8, IL-18, IL-1β, IL-10, and IL-1ra; vascular endothelial growth factor (VEGF); granulocyte macrophage colony-stimulating factor (GM-CSF); and erythropoietin (EPO).
Results:
Ninety-four infants were recruited including age-matched controls (n = 10), DS/CHD (n = 55), and CHD only (n = 29). Children with DS/CHD had significantly lower concentrations of several cytokines (IL-10, IL-6, IL-8, IL-1β, VEGF) in the pre- and post-operatively vs CHD only and controls. EPO and GM-CSF were significantly higher in DS/CHD (p value <0.05).
Conclusions:
Children with DS/CHD had significantly lower concentrations of several cytokines compared to controls or children with CHD only. EPO and GM-CSF were significantly higher in children with DS/CHD. The assessment of the immune response may be suitable for the predictable clinical outcomes in these children.
Impact:
This study demonstrated that children with Down syndrome (DS) and congenital heart disease (CHD) have significant alterations in pro-inflammatory and anti-inflammatory immune responses peri-operatively. These changes may contribute to adverse clinical outcomes, including sepsis, chylothorax, and autoimmunity. They may impact the pathogenesis and outcome post-operatively and long term in this population. Children with DS and CHD have significantly lower cytokine concentrations, increased EPO and GM-CSF, and decreased VEGF pre- and post-operatively. Assessing their inflammatory state peri-operatively may facilitate the development of a predictive model that can inform tailored management of these infants using novel therapies including immunomodulation.
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