Depressed AIRE Gene Expression Causes Immune Cell Dysfunction & Autoimmunity in Down Syndrome

This study plans to learn more about Down syndrome. The investigators think there is a different level of the AIRE gene in individuals with Down syndrome. The investigators think that the AIRE gene level can provide more insight about depressed immune cell function in individuals with Down syndrome. Patients are being asked to be in this research study because the investigators want to see if their blood contains more of less of the AIRE gene.

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Infections; Down Syndrome; Polyendocrinopathies, Autoimmune; Autoimmunity
• Intervention / Treatment: Other: Phlebotomy

Detailed Description

Down Syndrome (DS) is the most common chromosomal abnormality among live-born infants. Through full or partial trisomy of chromosome 21, DS is associated with cognitive impairment, congenital malformations (particularly cardiovascular), and dysmorphic features. In addition, immunological abnormalities are much more prevalent in individuals with DS. For example, DS is associated with increased susceptibility to infection, as revealed in 2009 during the influenza pandemic where the likelihood of death was 300 times greater for DS patients than the general population. DS patients have increased frequencies of autoimmune disorders and leukemias, yet curiously, have a decreased risk for allergic diseases, particularly asthma. Perhaps the most telling statistic for immunologic abnormality in DS patients is that respiratory tract infections are the most important cause of mortality in DS at all ages.Our studies have identified AIRE as a master control gene that is aberrantly decreased in persons with DS, leading to autoimmunity and immunologic abnormalities. AIRE ("autoimmune regulator"), although encoded on chromosome 21, is also significantly reduced in expression in DS, where it may contribute to autoimmune and immune dysregulation. The investigators will test the hypothesis that immune dysfunction and autoimmune disease preferentially occur in DS as a consequence of deficient expression of AIRE in peripheral blood cells.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado, Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 22 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age newborn up until the twenty-second birthday.
2. Diagnosed with idiopathic or secondary pulmonary arterial hypertension as defined by a mean pulmonary artery pressure > 25 mmHg at rest or > 30 mmHg with exercise.
3. Confirmed trisomy 21.
4. Followed by the Pulmonary Hypertension Program and Sie Center at The Children's Hospital.
5. The investigator or co-investigator must obtain written informed consent and assent where applicable before any study procedure is performed or data is collected.

Exclusion Criteria:

1. Any person older than 22 years of age
2. Patients with sickle cell disease with Pulmonary Arterial Hypertension (PAH) as treatment is defined differently within this population.
3. In the opinion of the investigator, a patient who is unlikely to cooperate or complete the study for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Persons without Down syndrome; White blood cell analysis from persons without Down syndrome assessed by absence of trisomy 21.	Other: Phlebotomy; White blood cell analysis: Subtypes of white blood cells will be counted by flow cytometry
OTHER: Persons with Down syndrome; White blood cell analysis from persons with Down syndrome assessed by presence of trisomy 21.	Other: Phlebotomy; White blood cell analysis: Subtypes of white blood cells will be counted by flow cytometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AIRE Gene expression in Macrophage Subpopulations	Peripheral blood draw	At the time of sample acquisition

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
White blood cell Subpopulation Numbers	Peripheral blood draw	At the time of sample acquisition

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Michael E Yeager, Ph.D., University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 19, 2015
• Primary Completion (ACTUAL): February 1, 2018
• Study Completion (ACTUAL): February 1, 2018

Study Registration Dates

• First Submitted: April 15, 2015
• First Submitted That Met QC Criteria: April 17, 2015
• First Posted (ESTIMATE): April 20, 2015

Study Record Updates

• Last Update Posted (ACTUAL): April 19, 2022
• Last Update Submitted That Met QC Criteria: April 15, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Infections; Respiratory Tract Diseases; Immune System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Down Syndrome; Respiratory Tract Infections; Autoimmune Diseases; Polyendocrinopathies, Autoimmune
• Other Study ID Numbers: 14-2300

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No