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

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ClinicalTrials.gov Identifier: NCT02421276
Recruitment Status : Recruiting
First Posted : April 20, 2015
Last Update Posted : May 17, 2017
Sponsor:
Information provided by (Responsible Party):

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
Down Syndrome Polyendocrinopathies, Autoimmune Respiratory Tract Infections Autoimmunity 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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 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 : October 19, 2015
Estimated Primary Completion Date : August 2017
Estimated Study Completion Date : September 2017


Arms and Interventions

Arm Intervention/treatment
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
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 [ Time Frame: At the time of sample acquisition ]
    Peripheral blood draw


Secondary Outcome Measures :
  1. White blood cell Subpopulation Numbers [ Time Frame: At the time of sample acquisition ]
    Peripheral blood draw


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02421276


Contacts
Contact: Kelley L Colvin, M.A. 3037244191 kelley.colvin@ucdenver.edu

Locations
United States, Colorado
University of Colorado, Denver Recruiting
Denver, Colorado, United States, 80045
Contact: Michael Yaeger         
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Michael E Yeager, Ph.D. University of Colorado, Denver
More Information

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02421276     History of Changes
Other Study ID Numbers: 14-2300
First Posted: April 20, 2015    Key Record Dates
Last Update Posted: May 17, 2017
Last Verified: May 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Down Syndrome
Syndrome
Respiratory Tract Infections
Autoimmune Diseases
Polyendocrinopathies, Autoimmune
Disease
Pathologic Processes
Infection
Respiratory Tract Diseases
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Immune System Diseases
Endocrine System Diseases