People with Down syndrome have a different disease spectrum compared to the typical population, but exactly why this is remains unclear. To begin addressing this, Drs. Kelly Sullivan and Tom Blumenthal employed proteomics approaches to analyze blood samples from 165 individuals with Down syndrome. They found dozens of proteins that are consistently deregulated by trisomy 21, including many proteins involved in immune control, the complement cascade, and growth factor signaling. Importantly, many of the immune-related protein changes observed resembled changes seen in type I interferonopathies and other autoinflammatory conditions. These results are consistent with the hypothesis that increased interferon signaling caused by trisomy 21 leads to chronic immune dysregulation.
Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation. Sullivan KD, Evans D, Pandey A, Hraha TH, Smith KP, Markham N, Rachubinski AL, Wolter-Warmerdam K, Hickey F, Espinosa JM, Blumenthal T. Scientific Reports. 2017 Nov 1;7(1):14818. PMID: 29093484.