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
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.