Natural History of Dysregulation and Aging of the Immune System in People With Trisomy 21 With and Without Thymectomy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 700
- 试验地点
- 1
- 主要终点
- Frequency of T21 individuals with laboratory evidence of autoantibodies
研究概览
简要总结
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.
详细描述
Study Description:
This is a longitudinal observational study of individuals with trisomy 21 (T21) to gather data on the immune function in order to identify clinical and laboratory signatures of immunodeficiency and/or immune dysregulation, characterize their pathophysiology, evaluate their progression and evolution over time, and analyze the impact of immunomodulatory and immunosuppressive treatment. In order to assess the possible impact of thymectomy on immune dysfunction and on the risk of developing autoimmunity, malignancies, and/or increased susceptibility to infections, both individuals who have had previous thymectomy and those who have not received this procedure will be included. Affected participants will have a baseline visit and follow-up study visits every year (starting from baseline) to assess their health and collect biospecimens (including but not limited to blood). Additional visits can also be scheduled as clinically indicated. Data and excess biospecimens from routine clinical care may also be collected and used for research. Unaffected relatives who live in the same household as the corresponding affected participant will be enrolled as controls and will undergo yearly blood and stool collection for comparison of microbiome and immunological data.
Objectives:
Primary Objectives:
- Describe the immune correlates of clinical endpoints (infections, development or progression of lung damage, 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
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Year 至 120 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •INCLUSION CRITERIA:
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •1. Aged >=1 year.
- •2. Willingness to allow storage of specimens and data for future research.
- •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
- •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.
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •1. 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.
研究组 & 干预措施
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
结局指标
主要结局
Frequency of T21 individuals with laboratory evidence of autoantibodies
时间窗: Through end of study
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
时间窗: Through end of study
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
时间窗: Through end of study
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
时间窗: Through end of study
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
Nature of infections (bacterial, viral, fungal, opportunistic pathogens) requiring hospitalization
时间窗: Through end of study
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
Incidence of severe infections requiring hospital admission (number of admissions/year; number of days of hospitalization/year)
时间窗: Through end of study
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
次要结局
- Proportion of dysreactive B cell subsets (defined as CD19(hi) CD21(low) CD38(low) B cells)(Through end of study)
- 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)