An article published online in Scientific Reports shows that Down syndrome may be a form of chronic immune disorder. In the largest and most comprehensive study of its kind to date, investigators at the Crnic Institute for Down Syndrome, the Sie Center for Down Syndrome, the University of Colorado, and Somalogic measured the levels of over 3500 proteins in the blood of Down syndrome patients and compared them to non-Down syndrome controls. Their results provide a new framework for understanding the physiological mechanisms that drive the altered disease susceptibilities seen in individuals with Down syndrome, and suggest that individuals with Down syndrome could benefit from therapies that decrease or modulate immune responses.

Down syndrome, or Trisomy 21, is caused by having three copies of chromosome 21 instead of two. Although the genetics of Down syndrome have been known for 60 years, it is still unclear how having the extra chromosome leads to various Down syndrome traits, including changes in common disease susceptibilities (e.g., Down syndrome individuals are more likely to develop Alzheimer’s, leukemia and autoimmune disorders, but less likely to develop solid tumors and cardiovascular disease). Understanding the biology that underlies these differences could inform a wide range of medical conditions that affect not only Down syndrome individuals, but the entire population.

The researchers used the SOMAscan assay to compare levels of blood proteins in 165 individuals with Down syndrome and 98 controls, and they identified 299 proteins that differed significantly between the two groups. Surprisingly, most of these proteins are not encoded by genes located on chromosome 21, but are associated with immune system control. Down syndrome individuals appear to have something that resembles an autoinflammatory condition, with elevated levels of proteins that promote inflammation but deficiencies in proteins that help eliminate foreign pathogens. The findings provide a new way to think about Down syndrome and possible targets of therapies to improve the health and lifespan of those with Down syndrome as well as the general population.

Sullivan, KD et al. (2017) “Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation” Scientific Reports 7(1): 14818.