Genetic Risk Factors Associated With Antiphospholipid Antibody Syndrome

APS is an autoimmune disorder that causes an increased risk for developing a venous or
arterial thromboembolism, as well as recurrent miscarriages. APS frequently occurs in people
with lupus, and is referred to as secondary APS in this case. Many people who have APS,
however, do not have another autoimmune disorder, and their disease is referred to as primary
APS. APS may be a genetic disorder, and identifying the gene(s) that predisposes an
individual to develop it could lead to a better understanding of the disease, as well as
improved therapies. This study will use a genetic strategy to identify potential risk factors
for the development of APS by recruiting people with APS who have family members who are
either affected by the syndrome or who have another autoimmune disorder. The results of the
genetic testing will be compared among the following two groups of families: people with APS
who also have one or more of their family members affected specifically by APS; and people
with APS who also have one or more of their family members affected by another type of
autoimmune disorder, such as lupus or rheumatoid arthritis.

Participants in this study will perform a pre-screening questionnaire over the phone to
determine relevant clinical diagnoses and collect a brief family history of autoimmune
disorders. Eligible participants will receive an enrollment package in the mail. If possible,
participants will then report to the study site to supply a detailed family and medical
history and provide a blood sample for analysis for antiphospholipid antibodies and
preparation of genomic DNA. If participants are unable to attend the study visit, the
interviews will be conducted over the phone. Those who are unable to attend the site visit
will receive a blood enrollment kit in the mail, and these participants will report to a
convenient location for phlebotomy services. Participants who have already provided blood
samples for the APS Collaborative Registry (APSCORE) may not have to provide another sample
for this study. Information collected for statistical analysis will include the following
data: demographic information; co-morbid conditions and chronic risk factors; lipid profile;
history of recurrent infections, renal failure, and cardiovascular disease; height and
weight; details of any medications and supplements currently being taken; venous and arterial
thromboembolic events; and any history of adverse pregnancy outcomes.

Inclusion Criteria:

- Persistent presence of an antiphospholipid antibody, as defined by one or both of the
following criteria:

1. Medium or high anticardiolipin antibody level in the blood on two or more
occasions at least 6 weeks apart

2. Presence of lupus anticoagulant in the plasma on two or more occasions at least 6
weeks apart

- Presence of clinical symptoms seen in patients with APS, including vascular thrombosis
(one or more clinical episodes of arterial, venous, or small vessel thrombosis in any
tissue or organ) and/or pregnancy morbidity, defined as any of the following:

1. One or more unexplained deaths of a morphologically normal fetus at or beyond the
10th week of gestation, with normal fetus morphology documented by ultrasound or
direct examination or the fetus

2. One or more premature births of a morphologically normal baby at or before the
34th week of gestation because of severe pre-eclampsia, eclampsia, or severe
placental insufficiency

3. Three or more unexplained consecutive spontaneous abortions before the 10th week
of gestation, with maternal anatomic or hormonal abnormalities and paternal and
maternal chromosomal causes excluded

- People who have elevated antiphospholipid antibody levels but do not fully meet
clinical criteria for APS, and do have affected family members, will be considered for
enrollment

Exclusion Criteria:

- No documented presence of antiphospholipid antibody