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 5-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.

Population

1- Proband who have documented evidence that he/she meets criteria for adult and juvenile forms of systemic rheumatic disorders defined here as rheumatoid arthritis (RA), systemic lupus 2- Twin pair of the proband who does not meet criteria for one of the rheumatic diseases and is willing to give consent and enroll in the study 3- Sibling of the same biological parents, same gender, within 5 years of age of the proband who does not meet criteria for one of the rheumatic diseases and is willing to give consent and enroll in the study 4- Biological mother or father of the proband who is willing to enroll in the study 5- A healthy individual who has not used any anti-inflammatory medications, has not had an infectious disease(persistent or chronic infection, history of M. tuberculosis, HIV or active infection), or experienced severe trauma within 8 weeks of enrollment, doesn't have a first degree relatives with RA, SLE, SSc or IIM and is willing to participate in the study

Brief Title

Study of Families With Twins or Siblings Discordant for Rheumatic Disorders

Official Title

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

Brief Summary

This study will examine families in which one sibling of a sibling pair, or twin pair, has <br /> developed a systemic rheumatic disease and one has not, to see if and how the two differ in <br /> the following: <br /> <br /> - Blood cell metabolism; <br /> <br /> - Types of cells in the blood; <br /> <br /> - Environmental exposures or genetic factors that might explain why one developed disease <br /> and the other did not. <br /> <br /> Families in which one sibling has developed a systemic rheumatic disease, rheumatoid <br /> arthritis, systemic lupus erythematosus, scleroderma, dermatomyositis, or myositis, and the <br /> other has not, are eligible for this study. The siblings may or may not be twins, but must be <br /> of the same gender and be within a 5-year age difference. Biological parents, or, in some <br /> cases, children, will also be included in the study. Normal, healthy volunteers will serve as <br /> control subjects. <br /> <br /> Participants will undergo some or all of the following tests and procedures: <br /> <br /> - Medical history and physical examination. Participants will also be asked permission to <br /> obtain medical records for review. <br /> <br /> - Questionnaires about environmental exposures at work, at home, and elsewhere. Probands <br /> (participants with rheumatic disease) and their healthy siblings will also answer <br /> questions about infections, vaccinations, medications or dietary supplements, sun <br /> exposure, and stressful events during the year before disease diagnosis in the affected <br /> sibling. <br /> <br /> - Blood and urine collection for the following tests: <br /> <br /> - Routine blood chemistries and other studies to rule out certain diseases or medical <br /> problems; <br /> <br /> - Evidence of past toxic exposures and certain infections; <br /> <br /> - Presence of cells from the mother in the child s blood and vice versa. (Recent studies <br /> suggest that during pregnancy or delivery, cells from the mother and baby may be <br /> exchanged and circulate in the body for many years, possibly causing problems); <br /> <br /> - In twin or sibling pairs, presence of certain genes that may be more common in patients <br /> with systematic rheumatic diseases as compared with their unaffected siblings and normal <br /> volunteers; <br /> <br /> - In identical twins, comparison of their blood cell metabolism to see if and how the <br /> metabolism differs in people with rheumatic disease. <br /> <br /> Participants may be asked for permission to have some of their blood and urine samples stored <br /> and to obtain previously collected blood or tissue biopsy specimens that are no longer needed <br /> for clinical care, for research purposes. They may also be asked to give additional blood or <br /> urine samples. <br /> <br /> Participants will be followed every year for 5 years (either in person or by questionnaire) <br /> to evaluate any changes in their condition. The final 5-year evaluation will repeat some of <br /> the questionnaires and procedures described above.

Detailed Description

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 of more 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.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.