Increased systemic inflammation in children with Down syndrome

Kelly, Lynne; Ryan, Emer; McGrane, Fiona; Lagan, Niamh; Roche, Edna; Balfe, Joanne; Leahy, T. Ronan; Franklin, Orla; Doherty, Derek G.; Molloy, Eleanor J.

doi:10.1016/j.cyto.2019.154938

Cited by 68 publications

(56 citation statements)

References 52 publications

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“…There is evidence that IL-10 is elevated in DS, and it is hypothesized that the pronounced anti-inflammatory signals could be a contributor in the increased prevalence of respiratory tract infections and pneumococcal lung disease (32,97). We found that at baseline children with DS had greater levels of both pro-(IL-2, IL-6) and anti-inflammatory cytokines (IL-10, IL-1ra), as well as other mediators (Epo, VEGF, GM-CSF) (98). This demonstrates a cohort exhibiting both a potent pro and anti-inflammatory phenotype which again may contribute to the worse outcomes in sepsis and the increased prevalence of chronic disease and autoimmunity.…”

Section: Cytokinesmentioning

confidence: 76%

Immune Dysregulation in Children With Down Syndrome

Huggard

Doherty

2020

Front. Pediatr.

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Section: Cytokinesmentioning

confidence: 76%

Immune Dysregulation in Children With Down Syndrome

Huggard

Doherty

2020

Front. Pediatr.

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“…Fragmented and bioenergetically inefficient mitochondria have also been observed in DS as a result of impaired MQC [163]. Along with these changes, signs of premature immunosenescence (i.e., lower activity of natural killer cells, reduced repertoire of T and B lymphocytes, telomere erosion in lymphocytes, and increased risk of developing autoimmune disorders) and a pro-inflammatory profile characterize people with DS [164,165].…”

Section: Down Syndromementioning

confidence: 99%

Mitochondrial Dysfunction, Oxidative Stress, and Neuroinflammation: Intertwined Roads to Neurodegeneration

et al. 2020

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Oxidative stress develops as a response to injury and reflects a breach in the cell’s antioxidant capacity. Therefore, the fine-tuning of reactive oxygen species (ROS) generation is crucial for preserving cell’s homeostasis. Mitochondria are a major source and an immediate target of ROS. Under different stimuli, including oxidative stress and impaired quality control, mitochondrial constituents (e.g., mitochondrial DNA, mtDNA) are displaced toward intra- or extracellular compartments. However, the mechanisms responsible for mtDNA unloading remain largely unclear. While shuttling freely within the cell, mtDNA can be delivered into the extracellular compartment via either extrusion of entire nucleoids or the generation and release of extracellular vesicles. Once discarded, mtDNA may act as a damage-associated molecular pattern (DAMP) and trigger an innate immune inflammatory response by binding to danger-signal receptors. Neuroinflammation is associated with a large array of neurological disorders for which mitochondrial DAMPs could represent a common thread supporting disease progression. The exploration of non-canonical pathways involved in mitochondrial quality control and neurodegeneration may unveil novel targets for the development of therapeutic agents. Here, we discuss these processes in the setting of two common neurodegenerative diseases (Alzheimer’s and Parkinson’s disease) and Down syndrome, the most frequent progeroid syndrome.

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“…However, the molecular mechanisms leading to the immune defects observed in DS individuals and the contribution of these immunological abnormalities remain largely unknown, especially in DS prepubertal children [55]. Children with Down Syndrome develop more infections, have an increased mortality from sepsis, and an increased incidence of chronic inflammatory conditions [56]. Cytokine dysregulation may underpin these clinical sequelae and raised proinflammatory biomarkers are a feature in adults with DS [56].…”

mentioning

confidence: 99%

“…Children with Down Syndrome develop more infections, have an increased mortality from sepsis, and an increased incidence of chronic inflammatory conditions [56]. Cytokine dysregulation may underpin these clinical sequelae and raised proinflammatory biomarkers are a feature in adults with DS [56]. Changes in young and adult DS individuals' immune response is modulated by the levels of pro-and anti-inflammatory cytokines [57,58] depending on many factors as the severity and extension of the trisomy 21, the presence of concomitant immunological disorders, infections, age, oxidative stress, congenital heart diseases, neurological impairments, and blood/nonblood cancers [59,60].…”

mentioning

confidence: 99%

Neuroinflammatory Markers in the Serum of Prepubertal Children with Down Syndrome

Tarani

Carito

Ferraguti

et al. 2020

Journal of Immunology Research

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Down Syndrome (DS) is the most common chromosomal disorder. Although DS individuals are mostly perceived as characterized by some distinct physical features, cognitive disabilities, and cardiac defects, they also show important dysregulations of immune functions. While critical information is available for adults with DS, little literature is available on the neuroinflammation in prepubertal DS children. We aimed to evaluate in prepubertal DS children the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), oxidative stress as free oxygen radicals defense (FORD), free oxygen radicals test (FORT), and cytokines playing key roles in neuroinflammation and oxidative processes as TNF-α, TGF-β, MCP-1, IL-1α, IL-2, IL-6, IL-10, and IL-12. No differences were found in NGF between DS children and controls. However, BDNF was higher in DS subjects compared to controls. We also did not reveal changes in FORD and FORT. Quite interestingly, the serum of DS children disclosed a marked decrease in all analyzed cytokines with evident differences in serum cytokine presence between male and female DS children. In conclusion, the present study evidences in DS prepubertal children a disruption in the neurotrophins and immune system pathways.

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Increased systemic inflammation in children with Down syndrome

Cited by 68 publications

References 52 publications

Immune Dysregulation in Children With Down Syndrome

Immune Dysregulation in Children With Down Syndrome

Mitochondrial Dysfunction, Oxidative Stress, and Neuroinflammation: Intertwined Roads to Neurodegeneration

Neuroinflammatory Markers in the Serum of Prepubertal Children with Down Syndrome

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