• 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 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. 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 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 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+.