Natural History of Dysregulation and Aging of the Immune System in People With Trisomy 21 With and Without Thymectomy

NCT07416201 | Recruiting

• 2 other identifiers: 10002372002372-I
• Study Type: observational
• Target: 700
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Down Syndrome

Keywords

Down Syndrome; Immunologic Deficiency Syndromes; THYMECTOMY

Outcome Measures

Primary Outcomes (6)

• 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

  Through end of study

• 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

  Through end of study

• 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

  Through end of study

• 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

  Through end of study

• Nature of infections (bacterial, viral, fungal, opportunistic pathogens) requiring hospitalization

  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

  Through end of study

• Incidence of severe infections requiring hospital admission (number of admissions/year; number of days of hospitalization/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

  Through end of study

Secondary Outcomes (5)

• Levels of specific antibodies to immunization antigens

  Through end of study

• Proportion of T cells exhibiting expression of exhaustion markers

  Through end of study

• Diversity of T-cell receptor repertoire, measured as proportion of CD4+ and CD8+ cells expressing distinct TRBV families

  Through end of study

• Distribution of subsets of Th, T follicular helper, and Treg cells

  Through end of study

• Proportion of dysreactive B cell subsets (defined as CD19(hi) CD21(low) CD38(low) B cells)

  Through end of study

Study Arms (2)

Trisomy 21 Participants

Participants aged \>=1 year old who have T21

Unaffected Relative Participants

Participants aged \>=1 year old who are related to a participant with T21

Eligibility Criteria

• Age: 1 Year - 120 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• \. Aged \>=1 year.
• \. Willingness to allow storage of specimens and data for future research.
• Documented T21 based on chromosomal karyotype test.
• Ability of participant or LAR to provide informed consent.
• Ability of participant to provide informed consent or, for individuals \<18 years of age, to provide informed assent as applicable.
• Reside in the same household as the corresponding affected participant.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• \. Any condition that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Down Syndrome; Immunologic Deficiency Syndromes

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Immune System Diseases

Study Officials

• Luigi D Notarangelo, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luigi D Notarangelo, M.D.

CONTACT

(301) 761-7550; luigi.notarangelo2@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2026
• First Posted: February 18, 2026
• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): May 1, 2040
• Study Completion (Estimated): November 1, 2040
• Last Updated: April 16, 2026

Record last verified: 2026-03-25

Data Sharing

• IPD Sharing: Will share
• Time Frame: In preparation of publication, data will be deposited on data sharing platforms (such as Zenodo, Github, ImmPort, dbGaP) with an embargo until publication date, and access codes that will be made available to reviewers of the manuscript.
• Access Criteria: Unpublished data will be made available upon written request and according to a data sharing agreement approved by the Office of Technology Transfer and Intellectual Property, National Institutes of Health.@@@@@@When included in publications, these data will be made available as part of the Supporting Information associated with the manuscript.@@@@@@

Locations

US (1)