According to the CDC, each year, about 6,000 infants are born with Down syndrome in the United States. Between 1979 and 2003, the number of babies born with Down syndrome increased by about 30% in the U.S. Older moms are more likely to have a child impacted by Down syndrome than younger mothers.
” Usually too much swelling means autoimmune illness, and immune suppression typically indicates susceptibility to infections,” says senior research study author Dusan Bogunovic of the Icahn School of Medicine at Mount Sinai. “What is uncommon is that people with Down syndrome are both immunosuppressed and swollen, a paradox of sorts. Here, we discovered how this is possible.”
Down syndrome is normally brought on by the triplication of chromosome 21. This syndrome affects several organ systems, causing a combined clinical discussion that includes intellectual impairment, developmental hold-ups, congenital heart and gastrointestinal problems, and Alzheimers illness in older people.
Oscillations of hyper- and hypo-response to the powerful cytokine IFN-I in people with Down syndrome incline to both lower incidence of viral illness and increased infection-related morbidity and death. New findings reveal why people with Down syndrome have less frequent, however more serious viral infections.
In between 1979 and 2003, the number of children born with Down syndrome increased by about 30% in the U.S. Older mothers are more likely to have a child impacted by Down syndrome than younger mothers.
” We have a lot more to do to totally comprehend the intricacies of the body immune system in Down syndrome.”– Louise Malle
Oscillations of hyper- and hypo-response to the potent cytokine IFN-I in people with Down syndrome incline to both lower incidence of viral disease and increased infection-related morbidity and death. Credit: Immunity/Malle et al
. New findings reveal why people with Down syndrome have less frequent, but more serious viral infections.
Individuals with Down syndrome have less-frequent viral infections. Elevated IFN-I levels lead to hyperactivity of the immune action at first, but the body overcorrects for this to reduce swelling, leading to increased vulnerability later on in the viral attack.
While individuals with Down syndrome reveal clear signs of immune disruption, it has yet to be clarified how a supernumerary chromosome 21 leads to dysregulation of viral defenses. Taken together, the findings reveal oscillations of hyper- and hypo-responses to IFN-I in Down syndrome, inclining to both lower incidence of viral illness and increased infection-related morbidity and death.
Just recently, it has ended up being clear that irregular antiviral responses are another essential feature of Down syndrome. Increased rates of hospitalization of people with Down syndrome have been documented for influenza A virus, breathing syncytial infection, and extreme intense breathing syndrome due to coronavirus (SARS-CoV-2) infections.
While people with Down syndrome reveal clear indications of immune disturbance, it has yet to be illuminated how a supernumerary chromosome 21 leads to dysregulation of viral defenses. To resolve this understanding space, the scientists compared fibroblasts and leukocyte originated from individuals with and without Down syndrome, at both the mRNA and protein levels. They concentrated on the powerful antiviral cytokine IFN-I receptor subunits IFNAR1 and IFNAR2, which are situated on chromosome 21.
The scientists found that increased IFNAR2 expression was enough for the hypersensitivity to IFN-I observed in Down syndrome, independent of trisomy 21. Taken together, the findings reveal oscillations of hyper- and hypo-responses to IFN-I in Down syndrome, predisposing to both lower incidence of viral illness and increased infection-related morbidity and mortality.
” We have a lot more to do to entirely comprehend the complexities of the immune system in Down syndrome,” says initially author Louise Malle of the Icahn School of Medicine at Mount Sinai. “We have here, in part, described the susceptibility to serious viral illness, however this is only the tip of the iceberg.”
Reference: “Excessive Negative Regulation of Type I Interferon Disrupts Viral Control in Individuals with Down Syndrome” by Louise Malle, Marta Martin-Fernandez, Sofija Buta, Ashley Richardson, Douglas Bush and Dusan Bogunovic, 14 October 2022, Immunity.DOI: 10.1016/ j.immuni.2022.09.007.