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.
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.
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
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.
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.