Protocol Number: 03-E-0099

Title:

Pathogenic Studies In Families With Twins Or Siblings Discordant For Systemic Rheumatic Disorders

Number:

03-E-0099

Summary:

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 the following:

- 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 sibling.

- Blood and urine collection for the following tests:

- Routine blood chemistries and other studies to rule out certain diseases or medical problems;

- 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 normal volunteers;

- 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.

Sponsoring Institute:

National Institute of Environmental Health Sciences (NIEHS)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

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 (less than 18 years of age) or adults (18 or more years of age) require a diagnosis of a systemic rheumatic disorder or other criteria for the adult or juvenile forms of RA, SLE, SSc, or IIM. Regarding the childhood-onset diseases: JRA will be defined by age of onset less than 17 years of age; for other diseases age of onset will be less than 18 years. Probands will be diagnosed within 3 years of enrollment in the study, with at least one twin or other sibling of the same gender within 3 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.

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 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. Those 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

Exclusion criteria for all 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 judgement 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 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 Vitiligo).

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+.

Special Instructions: Currently Not Provided

Keywords:

Autoimmunity Pathogenesis

Microarray Analyses

Microchimerism

Genetic and Environmental Risk Factors

Adult And Pediatric Disease

Rheumatoid Arthritis

Systemic Lupus Erythematosus

Systemic Sclerosis

Idiopathic Inflammatory Myopathies

Recruitment Keywords:

Inflammatory Myopathies

Dermatomyositis

Scleroderma

Systemic Lupus Erythematosus

SLE

Lupus

Rheumatic Disease

Rheumatoid Arthritis

RA

Healthy Volunteer

HV

Conditions:

Rheumatic Diseases

Rheumatoid Arthritis

Systemic Lupus Erythematosus

Scleroderma

Dermatomyositis

Myositis

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Todd JA. Human genetics. Tackling common disease.

Nature. 2001 May 31;411(6837):537, 539. No abstract available.

Jury EC, D'Cruz D, Morrow WJ. Autoantibodies and overlap syndromes in autoimmune rheumatic disease. J Clin Pathol. 2001 May;54(5):340-7. Review.

Shamim EA, Miller FW. Familial autoimmunity and the idiopathic inflammatory myopathies. Curr Rheumatol Rep. 2000 Jun;2(3):201-11. Review.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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