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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT02421276
• Collaborator: (none)
• Enrollment: 45
• Location: 1
• Arms: 2
• Actual Duration (Months): 27.5
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Down Syndrome; Polyendocrinopathies, Autoimmune; Respiratory Tract Infections; Autoimmunity	Other: Phlebotomy	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Depressed AIRE Gene Expression Causes Immune Cell Dysfunction & Autoimmunity in Down Syndrome
• Actual Study Start Date: Oct 19, 2015
• Actual Primary Completion Date: Feb 1, 2018
• Actual Study Completion Date: Feb 1, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. AIRE Gene expression in Macrophage Subpopulations [At the time of sample acquisition]

   Peripheral blood draw

Secondary Outcome Measures

1. White blood cell Subpopulation Numbers [At the time of sample acquisition]

   Peripheral blood draw

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 22 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado, Denver	Denver	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02421276
• Other Study ID Numbers: 14-2300
• First Posted: Apr 20, 2015
• Last Update Posted: Apr 19, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Respiratory Tract Infections; Down Syndrome; Polyendocrinopathies, Autoimmune; Autoimmune Diseases; Syndrome

Study Results

No Results Posted as of Apr 19, 2022