Infants with Down syndrome and congenital heart disease have altered peri-operative immune responses.

Abstract

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.

• Authors: Lyudmyla Zakharchenko, Afif El-Khuffash, Tim Hurley, Lynne Kelly, Ashanti Melo, Maureen Padden, Orla Franklin, Eleanor J Molloy
• Journal: Pediatric research (Pediatr Res) Vol. 92 Issue 6 Pg. 1716-1723 (12 2022) ISSN: 1530-0447 [Electronic] United States
• PMID: 35352006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Granulocyte-Macrophage Colony-Stimulating Factor
• Interleukin-10
• Vascular Endothelial Growth Factor A
• Interleukin-6
• Interleukin-8
• Cytokines

Topics

• Child
• Humans
• Infant
• Granulocyte-Macrophage Colony-Stimulating Factor
• Interleukin-10
• Vascular Endothelial Growth Factor A
• Down Syndrome
• Interleukin-6
• Interleukin-8
• Cytokines (metabolism)
• Immunity
• Heart Defects, Congenital (surgery)