Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation

Sullivan, Kelly D.; Evans, Donald L.; Pandey, Ahwan; Hraha, Thomas; Smith, Keith P; Markham, Neil E.; Rachubinski, Angela L.; Wolter‐Warmerdam, Kristine; Hickey, Francis; Espinosa, Joaquín M.; Blumenthal, Thomas

doi:10.1038/s41598-017-13858-3

Cited by 172 publications

(173 citation statements)

References 93 publications

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“…Interestingly, in this previous report when these inflammatory markers were combined with measures of Aβ, they predicted AD development 15 . In further support of our findings, another report describes increased IL-6, VEGF-A, MCP-1, IL-22, and TNFα, but not other cytokines, in adults aged 20-65 with DS 55 . In contrast, a previous study of adults (mean age 30 years in DS and controls) found elevated serum MIP-1α, but not IFNγ, TNFα, MIP-1β, RANTES, or IL-6 56 .…”

Section: Discussionsupporting

confidence: 91%

Altered Relationship between Soluble TREM2 and Inflammatory Markers in Young Adults with Down Syndrome

Weber

Koenig

Khrestian

et al. 2019

Preprint

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Individuals with Down syndrome (DS) develop Alzheimer's disease (AD) -related neuropathology, characterized by amyloid plaques with amyloid β (Aβ) and neurofibrillary tangles with tau accumulation more frequently and at an earlier age than their neurotypical counterparts. Peripheral inflammation and the innate immune response are elevated in DS. Triggering receptor expressed in myeloid cells 2 (TREM2) genetic variants are risk factors for AD and other neurodegenerative diseases. A soluble cleavage product of TREM2 (sTREM2) has been described as elevated in AD cerebrospinal fluid and positively correlates with Aβ and cognitive decline. There is relatively little information about TREM2 in DS. The objective of this study was to examine the relationship between sTREM2 and inflammatory markers in DS, prior to the development of dementia symptoms. Since TREM2 plays a role in the innate immune response and has been associated with dementia, the hypothesis of this exploratory study was that young adults with DS pre-dementia (n=15, mean age 29.5 years) would exhibit a different relationship between sTREM2 and inflammatory markers in plasma, compared to neurotypical, agematched controls (n=16, mean age 29.6 years). Indeed, young adults with DS had significantly elevated plasma sTREM2 and inflammatory markers. In addition, in young adults with DS, sTREM2 correlated positively with 24 of the measured cytokines, while there were no significant correlations in the control group. Hierarchical clustering of sTREM2 and cytokine concentrations also differed between the group with DS and controls, supporting the hypothesis that its function is altered in people with DS predementia. This exploratory study provides a basis for future studies investigating the relationship between TREM2 and the broader immune response pre-dementia.

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Section: Discussionsupporting

confidence: 91%

Altered Relationship between Soluble TREM2 and Inflammatory Markers in Young Adults with Down Syndrome

Weber

Koenig

Khrestian

et al. 2019

Preprint

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“…Considering the potential role of IL‐10 in acquisition of tolerance, the defect in IL‐10 might contribute to delay in FPIES resolution. Increased TNF‐α in Down syndrome patients might confer predisposition to FPIES …”

Section: Different Phenotypes Of Food Protein‐induced Enterocolitis Smentioning

confidence: 99%

“…Increased TNF-α in Down syndrome patients might confer predisposition to FPIES. 46,47 T cells have long been incriminated in the FPIES pathophysiology. 48,49 However, although higher proliferation of peripheral mononuclear cells (PBMCs) after stimulation with the causal antigen has been found in CM-FPIES patients compared to controls, a large overlap was found between the groups.…”

Section: Pathophysiology Of Food Protein-induced Enterocolitis Syndmentioning

confidence: 99%

Food protein‐induced enterocolitis syndrome

Caubet

Cianferoni

Groetch

et al. 2019

Clin Experimental Allergy

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Food protein‐induced enterocolitis syndrome (FPIES) is a non‐IgE‐mediated gastrointestinal food allergic disorder that has gained a major interest the past decade. FPIES prevalence, which still needs to be accurately determine in different populations, appears to be higher than previously thought (ie up to 0.7% in infants in the 1st year of life). FPIES to seafood in adults is also increasingly reported; limited data suggest that adult FPIES is most commonly triggered by shellfish, tends to affect females more than men, is characterized by a significant delay in diagnosis and a prolonged course. The first international consensus guidelines on diagnosis and management of FPIES have been published in 2017, proposing new diagnostic criteria as well as new criteria for a positive oral food challenge. However, there is a need to develop new biomarkers to improve the diagnosis and management of FPIES patients, and this requires a better understanding of the pathophysiology. Recently, the role of T cells has been questioned and a major role of innate immune cells has been suggested in acute FPIES. Regarding the treatment of acute FPIES reaction, ondansetron has emerged as an adjunct to intravenous rehydration in moderate‐severe reactions and as a first‐line treatment in mild reactions. Important information regarding the nutritional management of FPIES patients that might be complex has also been provided in the international guidelines. In this review, we discuss recent advances regarding all those different aspects.

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“…4e). Finally, we used public datasets and summary statistics from SomaScan proteomic studies focusing on agerelated diseases including Alzheimer's Disease (AD) 26 , Down Syndrome (DS) 27 and cardiovascular disease (CVD) 28 . A proteomic study predicting body mass index (BMI) 29 based on the plasma proteome was used as a control since weight gain varies widely with age according to data from the US National Health and Nutrition Examination Study 30 ( Supplementary Fig.…”

Section: Proteins Linked To Age-related Diseases Are Enriched In Distmentioning

confidence: 99%

Undulating changes in human plasma proteome across lifespan are linked to disease

Lehallier

Gate

Schaum

et al. 2019

Preprint

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Aging is the predominant risk factor for numerous chronic diseases that limit healthspan. Mechanisms of aging are thus increasingly recognized as therapeutic targets. Blood from young mice reverses aspects of aging and disease across multiple tissues, pointing to the intriguing possibility that age-related molecular changes in blood can provide novel insight into disease biology. We measured 2,925 plasma proteins from 4,331 young adults to nonagenarians and developed a novel bioinformatics approach which uncovered profound non-linear alterations in the human plasma proteome with age. Waves of changes in the proteome in the fourth, seventh, and eighth decades of life reflected distinct biological pathways, and revealed differential associations with the genome and proteome of age-related diseases and phenotypic traits. This new approach to the study of aging led to the identification of unexpected signatures and pathways of aging and disease and offers potential pathways for aging interventions.

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Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation

Cited by 172 publications

References 93 publications

Altered Relationship between Soluble TREM2 and Inflammatory Markers in Young Adults with Down Syndrome

Altered Relationship between Soluble TREM2 and Inflammatory Markers in Young Adults with Down Syndrome

Food protein‐induced enterocolitis syndrome

Undulating changes in human plasma proteome across lifespan are linked to disease

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