This study will examine families in which one sibling of a sibling pair, or twin pair, has
developed a systemic rheumatic disease and one has not, to see if and how the two differ in
- Blood cell metabolism;
- Types of cells in the blood;
- Environmental exposures or genetic factors that might explain why one developed disease
and the other did not.
Families in which one sibling has developed a systemic rheumatic disease, rheumatoid
arthritis, systemic lupus erythematosus, scleroderma, dermatomyositis, or myositis, and the
other has not, are eligible for this study. The siblings may or may not be twins, but must
be of the same gender and be within a 3-year age difference. Biological parents, or, in
some cases, children, will also be included in the study. Normal, healthy volunteers will
serve as control subjects.
Participants will undergo some or all of the following tests and procedures:
- Medical history and physical examination. Participants will also be asked permission to
obtain medical records for review.
- Questionnaires about environmental exposures at work, at home, and elsewhere. Probands
(participants with rheumatic disease) and their healthy siblings will also answer
questions about infections, vaccinations, medications or dietary supplements, sun
exposure, and stressful events during the year before disease diagnosis in the affected
- Blood and urine collection for the following tests:
- Routine blood chemistries and other studies to rule out certain diseases or medical
- Evidence of past toxic exposures and certain infections;
- Presence of cells from the mother in the child's blood and vice versa. (Recent studies
suggest that during pregnancy or delivery, cells from the mother and baby may be
exchanged and circulate in the body for many years, possibly causing problems);
- In twin or sibling pairs, presence of certain genes that may be more common in patients
with systematic rheumatic diseases as compared with their unaffected siblings and
- In identical twins, comparison of their blood cell metabolism to see if and how the
metabolism differs in people with rheumatic disease.
Participants may be asked for permission to have some of their blood and urine samples
stored and to obtain previously collected blood or tissue biopsy specimens that are no
longer needed for clinical care, for research purposes. They may also be asked to give
additional blood or urine samples.
Participants will be followed every year for 5 years (either in person or by questionnaire)
to evaluate any changes in their condition. The final 5-year evaluation will repeat some of
the questionnaires and procedures described above.
|Ages Eligible for Study:||N/A|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||Accepts Healthy Volunteers|
- INCLUSION CRITERIA:
The minimum inclusion criteria needed for enrollment are a twin pair or sibling pair, as
defined by an eligible proband and his/her eligible twin or sibling, willing and able to
give informed consent, to enroll in the study, to complete the questionnaires and to
donate blood and urine samples (in case of children, parent/legal guardian must also be
willing and able to provide informed consent).
Proband inclusion criteria:
-Children (< 18 years of age) or adults (18 or more years of age) require a diagnosis of
a systemic rheumatic disorder (by American College of Rheumatology (ACR) or other criteria
for the adult or juvenile forms of RA, SLE, SSc, or IIM (per (92;93). Regarding the
childhood-onset diseases: JRA will be defined by age of onset < 17 years of age; for
other diseases age of onset will be < 18 years. Probands will be diagnosed within 4
years of enrollment in the study, with at least one twin or other sibling of the same
gender within 4 years of age and without a recognized systemic rheumatic disorder or other
autoimmune disease available for study.
Twin-sibling inclusion criteria:
-Children or adults who are twins or other siblings of a proband sharing the same
biological parents, but without a recognized systemic rheumatic or autoimmune disorder, of
the same gender and within 3 years of age of the proband. If monozygotic twins are
enrolled from a family, another unaffected non-twin sibling sharing the same biological
parents will be enrolled for each proband if available to allow for log-linear genetic
analyses. All probands and unaffected siblings need to be at least one year of age at the
time of autoimmune disease diagnosis. In the case of triplets or greater multiples, all
such siblings are eligible for enrollment.
Parent inclusion criteria:
-Individuals who are the genetic father and mother of the proband and twin-sib. Both
parents will be enrolled whenever possible.
Normal volunteer inclusion criteria:
-Healthy controls, recruited in part via the NIH Normal Volunteers program, and age-
(within 5 years in adults and 2 years in children), gender- and race-matched to a subset
of probands as controls needed for specific studies. Normal volunteers should be in good
health, without a recognized systemic rheumatic disorder or other autoimmune disease, and
should not be taking anti-inflammatory medicines, including nonsteroidal anti-inflammatory
drugs (NSAIDs) or corticosteroids.
Offspring of microchimeric women criteria:
-Biological offspring of women who are probands and are found to be microchimeric. These
offspring will be enrolled as normal volunteers in an attempt to confirm the source of
their mothers' microchimerism.
For all subjects:
-Ability of the subject or parents/legal guardians to provide informed consent to all
aspects of the study after full protocol information is provided.
Exclusion criteria for all protocol subjects:
1. active infections requiring therapy or alteration in daily occupation or antibiotics,
severe trauma or vaccinations within 8 weeks of enrollment
2. Still's disease/systemic-onset or pauciarticular JRA
3. medical illness that in the judgment of the investigators does not allow safe blood
draws or other clinical evaluations needed for study participation
4. cognitive impairment
5. inability to give informed assent or consent.
Exclusion criteria for twin-sibs:
-Not sharing the same biological parents (being half-brothers or half-sisters). Known
criteria for systemic rheumatic disease or autoimmune disease (for example: RA/JRA,
SLE/JSLE, SSc/JSSc, IIM/JIIM, Type 1 diabetes, Psoriasis, Still's disease/systemic-onset
or pauciarticular JRA, Celiac sprue, Autoimmune thyroid disease, Idiopathic
Thrombocytopenia Purpura, Multiple sclerosis, Myasthenia gravis, Systemic vasculitis or
Exclusion criteria for normal volunteers:
-Recognized systemic rheumatic disorder or other autoimmune disease, history of cancer or
taking anti-inflammatory medicines, including nonsteroidal anti-inflammatory drugs
(NSAIDs) or corticosteroids, severe trauma or vaccinations within 8 weeks, HIV+.