Study of Families With Twins or Siblings Discordant for Rheumatic Disorders

2014-08-27 03:55:28 | BioPortfolio


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.


Most autoimmune diseases are thought to develop as a result of chronic immune activation and dysregulation after selected environmental exposures in genetically susceptible individuals. Current evidence suggests that the adult and juvenile forms of systemic rheumatic disorders - defined here as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIM) - share many common clinical manifestations, immune responses, genetic, hormonal and environmental risk factors, and possible pathogeneses. Conversely, other studies imply that each rheumatic disease, as currently defined, may be composed more of homogeneous subgroups, known as elemental disorders, with different pathogeneses. This protocol will explore pathogenic mechanisms for systemic rheumatic disorders and possible elemental disorders through the evaluation of families with monozygotic or dizygotic twins or other siblings discordant for systemic rheumatic disorders (twin-sib pairs). Parents, normal volunteers and offspring of microchimeric female twin-sibs will also be evaluated as needed for the experimental designs of each portion of the protocol. A clinical evaluation, using standardized 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, who will make up 25-50% of the twin-sib pairs, and adults in similar ways to attempt to understand possible similarities and differences in pathogeneses of systemic rheumatic disorders based upon age of onset. Hypothesis-testing studies will assess differences in peripheral blood cell gene activation/suppression, levels and types of microchimerism between affected and unaffected individuals, selected genetic risk factors for these disorders and occupational and hormonal exposures hypothesized 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 better understand 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. Yearly follow-up of all twin-sib pairs for five years will be performed to assess clinical changes and a final comprehensive assessment will repeat the initial studies at five years after enrollment.

Study Design



Rheumatic Diseases


National Institutes of Health Clinical Center, 9000 Rockville Pike
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:55:28-0400

Clinical Trials [226 Associated Clinical Trials listed on BioPortfolio]

Rheumatic Diseases and Computer Use

Computers allow individuals to engage in economic, social, and entertainment activities. Despite the many benefits of computer use, many individuals with rheumatic diseases may have diffic...

Ocular Manifestations in Rheumatic Diseases

This is a search strategy for determining the prevalence of ocular complications in inflammatory rheumatic diseases for the purposes of a meta analysis.

Nurse-led Clinic for Patients With Rheumatic Diseases and Biological Treatment

Randomized controlled trial including 100 subjects with rheumatic diseases and biological treatment with a 28 point-Disease Activity Score(DAS28)3.2 or less. The subjects will be randomize...

Compliance of Traditional Chinese Medicine in Young Patients With Rheumatic Diseases

To evaluate the compliance of traditional Chinese medicine (TCM) in young people with Chronic rheumatic disease

Health Beliefs and Health Behaviors Among Minorities With Rheumatic Diseases

This study will explore the diverse health beliefs and behaviors among minority patients with rheumatic diseases. These diseases may cause joint pain, stiffness or swelling. Some can inv...

PubMed Articles [7727 Associated PubMed Articles listed on BioPortfolio]

Affected liver biochemistry in children with rheumatic diseases.

Children with rheumatic diseases often have elevated liver biochemistry. This can be triggered by medical treatment, e.g. methotrexate can induce liver injury ranging from mild to severe. Autoimmune h...

Differentiated laboratory diagnostics of rheumatic diseases.

Laboratory diagnostics of rheumatic diseases include examinations to confirm the diagnosis, estimate prognosis, assess disease activity as well as recognition and avoidance of complications. Although ...

Rapid glucocorticoid tapering therapy to reduce mortality from pneumocystis pneumonia in patients with rheumatic disease.

Pneumocystis pneumonia (PCP) is a serious complication in patients with rheumatic diseases who are receiving immunosuppressive therapy. These patients have a higher mortality from PCP than those with ...

Asymptomatic Rhabdomyolysis and Digital Necrosis-Clues for a Rheumatic Disease.

S100 proteins in rheumatic diseases.

Rheumatic diseases are characterized by sterile inflammation that causes severe long-term damage to various organ systems. A growing body of evidence supports a pivotal role for the pro-inflammatory c...

Medical and Biotech [MESH] Definitions

Cardiac manifestation of systemic rheumatological conditions, such as RHEUMATIC FEVER. Rheumatic heart disease can involve any part the heart, most often the HEART VALVES and the ENDOCARDIUM.

Physicians who specialize in treating RHEUMATIC DISEASES.

Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement.

A small round or oval, mostly subcutaneous nodule made up chiefly of a mass of Aschoff bodies and seen in cases of rheumatic fever. It is differentiated from the RHEUMATOID NODULE which appears in rheumatoid arthritis, most frequently over bony prominences. (From Dorland, 27th ed)

A benzyl-indazole having analgesic, antipyretic, and anti-inflammatory effects. It is used to reduce post-surgical and post-traumatic pain and edema and to promote healing. It is also used topically in treatment of RHEUMATIC DISEASES and INFLAMMATION of the mouth and throat.

More From BioPortfolio on "Study of Families With Twins or Siblings Discordant for Rheumatic Disorders"

Quick Search


Relevant Topics

Arthritis is by definition the inflammation of one or more joints, characterized by swelling, pain, warmth, redness and diminished range of joint movement (Oxford Medical Dictionary). There are many different types; Noninflammatory; Osteoarthritis, N...

Joint Disorders
A joint is where two or more bones come together, like the knee, hip, elbow, or shoulder. Joints can be damaged by many types of injuries or diseases, including Arthritis - inflammation of a joint causes pain, stiffness, and swelling with ...

Searches Linking to this Trial