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Your Environment. Your Health.

Pathogenic Studies in Families with Twins or Siblings Discordant for Systemic Rheumatic Disorders

Open for Recruitment

Study Background

Pathogenic Studies in Families with Twins or Siblings Discordant for Systemic Rheumatic Disorders

Open for Recruitment

Additional Information

Mother playing with her children
Study Flyer(890KB)

The goal of this study is to examine the genetic and environmental risk factors in the development of autoimmune diseases in twins and same-sex siblings, when one has an autoimmune disease and the other does not. Adults and children may enroll by completing questionnaires and donating blood and urine samples.

Current evidence suggests that the adult and juvenile forms of systemic rheumatic disorders - defined here as Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (Lupus; SLE), Systemic Sclerosis (Scleroderma; SSC), and Idiopathic Inflammatory Myopathies (Myositis; IIM) - share many common clinical manifestations, immune responses, genetic, hormonal and environmental risk factors, and possible causes. This protocol will explore the risk factors for systemic rheumatic disorders through the evaluation of families with monozygotic (identical) or dizygotic (fraternal) twins or other brothers or sisters (siblings) discordant for systemic rheumatic disorders (twin-sib pairs). Parents, normal volunteers will also be evaluated as needed for the experimental designs of each portion of the protocol.

For more information on this study, please visit the Clinical Trials Study webpage.

This content is available to use on your website.
Please visit NIEHS Syndication to get started.


Inclusion Criteria:

The minimum inclusion criteria needed for enrollment are a twin pair or sibling pair, as defined by a subject 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, the parent/legal guardian must also be willing and able to provide informed consent).

  1. Must be diagnosed with a systemic rheumatic disorder or other criteria for adult and juvenile forms of RA, SLE, SSC, or IIM
  2. Must be diagnosed within 5 years of study enrollment
  3. >1 years of age at the time of autoimmune disease diagnosis
  4. Individuals who are the genetic parents of the affected enrollee and his/her sibling

Inclusion Criteria, Unaffected Twin or Sibling:

  1. Must share the same biological parents with the affected sibling
  2. Must be of the same gender, within 5 years of age, and without a recognized systemic rheumatic disorder or other autoimmune disease

Exclusion Criteria:

  1. Exclusion criteria for persons affected by a systemic autoimmune disease
    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 Juvenile Idiopathic Arthritis
  2. Exclusion criteria for unaffected twins or siblings
    1. Not sharing the same biological parents (being half-brothers or half-sisters)
    2. Known criteria for systemic rheumatic disease or autoimmune disease in the unaffected twin or sibling: (for example: Rheumatoid arthritis, Juvenile rheumatoid arthritis, Lupus, Scleroderma, Myositis, Type 1 Diabetes, Psoriasis, Still's Disease, Celiac Sprue, Autoimmune Thyroid Disease, Idiopathic Thrombocytopenia Purpura, Multiple Sclerosis, Myasthenia Gravis, Systemic Vasculitis or Vitiligo)
    3. Active infections requiring therapy or alteration in daily occupation or antibiotics, severe trauma or vaccinations within 8 weeks of enrollment
  3. Exclusion criteria for normal volunteers
    1. Recognized systemic rheumatic disorder or other autoimmune disease
    2. History of cancer or taking chronic anti-inflammatory medicines, including nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids
    3. Active infections requiring therapy or alteration in daily occupation or antibiotics, severe trauma or vaccinations within 8 weeks of enrollment 

What will you do?

Adults or children are eligible to participate if they have been diagnosed with a systemic rheumatic disease (see above) within 5 years and they have a twin or same sex brother or sister who is healthy and within 5 years of age. Parents and matched normal volunteers will also be asked to participate. This is a blood, urine, and data collection study. A single enrollment /evaluation is all that is required. Evaluations include history and physical examinations and a number of blood tests. Blood and urine will also be collected for storage.

What will NIEHS do?

A clinical evaluation, using physician and patient clinical and environmental exposure questionnaires, and specimen collections from 400 twin-sib pairs discordant for systemic rheumatic disorders, will be performed to confirm diagnoses, document medical histories and assess possible risk factors implicated in the development of autoimmunity.

This study will evaluate children and adults in similar ways to attempt to understand possible similarities and differences in pathogeneses of systemic rheumatic disorders based upon age of onset. Studies will assess differences in peripheral blood cell gene activation/suppression, genetic risk factors for these disorders, and occupational, hormonal and other exposures thought to be potential risk factors for these diseases. Exploratory studies will be conducted to begin to assess other environmental risk factors for systemic rheumatic disorders and to gain a better understanding of associations among phenotypes and genotypes. Biologic specimens - including blood, urine, and other clinical specimens or biopsies no longer necessary for clinical care - will be collected for directed biomarker assays and the development of repositories for future research.

Study Location

Subjects may be enrolled at the NIH Clinical Center, 9000 Rockville Pike, Bethesda, MD, 20892, or at the NIEHS Clinical Research Unit, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, or in your local doctor's office.

Protocol Number: 03-E-0099

Enrollment and Contact Information

Referral/Patient Recruitment
Warren Grant Magnuson Clinical Center
National Institutes of Health
Bethesda, Maryland 20892-2655
Tel 800-411-1222, TTY 866-411-1010
Fax (301) 451-5588

Principal Investigator

Adult Subjects

Frederick W. Miller
Frederick W. Miller, M.D., Ph.D.
Deputy Chief, Clinical Research Branch and Principal Investigator
Tel 984-287-3593
Fax 301-451-5585
P.O. Box 12233
Mail Drop F1-09
Durham, N.C. 27709
Adam I. Schiffenbauer
Adam I. Schiffenbauer, M.D.
Staff Clinician
Environmental Autoimmunity Group, Clinical Research Branch
Tel 301-451-6270
10 Center Dr
Clinical Center Surgical Wing
Bethesda, MD 20892-1627

Pediatric Subjects

Lisa Rider, M.D.
Lisa Rider, M.D.
Deputy Chief and Staff Clinician, Environmental Autoimmunity Group
Tel 301-451-6272
Fax 301-480-2813
10 Center Dr
Hatfield Clinical Research Center
Bethesda, MD 20892-1301
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