Background:
Down syndrome is a genetic disorder that can cause heart defects and other problems in the body. People with Down syndrome are more likely to have infections, autoimmunity, and blood diseases. Some may need surgery to treat congenital heart problems. During this surgery, doctors sometimes remove part of the thymus. The thymus is an organ that plays a role in immune function. People who have had part of their thymus removed may get sick more often than others do.
Objective:
This natural history study will gather data about how removing part of the thymus affects the health of people with Down syndrome.
Eligibility:
People aged 1 year and older with Down syndrome. The study will include both people who have, and those who have not had, surgery to remove part of their thymus. Healthy relatives are also needed.
Design:
Participants with Down syndrome will have clinic visits at least once a year for 15 years.
At each visit they will have a physical exam. They will give blood and stool samples. They will have tests of their heart and lung function.
Participants aged 18 years or older may have at least 1 imaging scan: They will lie on a table that slides into a donut-shaped machine. The machine uses X-rays to take pictures of the inside of the body.
Participants who have tissue samples collected from their bodies (biopsies) taken during the study may have extra tissue taken for research.
Healthy relatives will also have visits once a year for 15 years. They will only have a physical exam and provide blood and stool samples.
Additional Inclusion Criteria for Affected Participants
Documented T21 based on chromosomal karyotype test.
Ability of participant or LAR to provide informed consent.
Additional Inclusion Criteria for Unaffected Relatives
None
Participants will be selected in an equitable manner from the available pool of potentially eligible individuals, without regard to factors such as sex, race, ethnicity, socioeconomic status, etc. To facilitate recruitment, the study will be registered in clinicaltrials.gov and will be shared with T21 advocacy groups.
Cohort
Prospective
Not listed
Frequency of T21 individuals with laboratory evidence of autoantibodies
Describe the immune correlates of clinical endpoints (infections, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21. Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Number and type of autoimmune manifestations/year
Describe the immune correlates of clinical endpoints (infections, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21. Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Frequency of individuals with abnormal T and B cell counts and immunoglobulin serum levels
Describe the immune correlates of clinical endpoints (infections, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21. Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Proportion of T21 individuals with malignancies by age group (compared to the general population), and type of malignancies
Describe the immune correlates of clinical endpoints (infections, autoimmunity, malignancies), and their cumulative frequency over time, in individuals with T21. Describe the possible impact of previous thymectomy on the incidence of clinical manifestations of immune deficiency and immune dysregulation, and on laboratory parameters of immune function
Levels of specific antibodies to immunization antigens
Identify cellular and molecular mechanisms of immune dysfunction in individuals with T21
Proportion of T cells exhibiting expression of exhaustion markers
Identify cellular and molecular mechanisms of immune dysfunction in individuals with T21
Diversity of T-cell receptor repertoire, measured as proportion of CD4+ and CD8+ cells expressing distinct TRBV families
Identify cellular and molecular mechanisms of immune dysfunction in individuals with T21
Distribution of subsets of Th, T follicular helper, and Treg cells
Identify cellular and molecular mechanisms of immune dysfunction in individuals with T21
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