Human Tumor Necrosis Factor Alpha (TNFa)-Induced Pre-B Cell Bone Marrow Emigrants

Inclusion Criteria: * Rheumatoid arthritis (RA) patients will be eligible for the study if they meet ACR criteria for a diagnosis of RA (Arnett et al. 1988. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis \& Rheumatism 31:315.) and have active disease (≥ 6 tender and/or swollen joints). * Subjects must be ≥ 18 years of age. * Subjects must be rheumatoid factor (RF) positive (any RF titer greater than the upper limits of normal) and/or anti-CCP antibody positive (any anti-CCP titer greater than the upper limits of normal). Subjects must have a negative TB skin test at entry into the study or a negative screening chest x-ray if the PPD test is inconclusive (borderline, reactive but non-diagnostic) or in prior BCG inoculated subjects. Female subjects of child bearing potential (excludes those that are surgically sterile or at least 5 years postmenopausal) must have a negative pregnancy test (serum β-HCG). Sexually active subjects of childbearing potential must agree to use medically acceptable forms of contraception during screening and throughout the study. * Subjects or a designee must have the ability to self-inject ENBREL or a care-giver at home who can administer subcutaneous injections. Subjects must be willing to remain on ENBREL (50 mg SQ qweek) for at least 12 weeks and have not taken anti-rheumatic agents (DMARDS and/or corticosteroids) besides NSAIDs for the previous 4 weeks. * The subject must be able and willing to give written informed consent and comply with the requirements of the study protocol and must authorize release and use of protected health information. Before any study-specific procedure, the appropriate written informed consent must be obtained. Exclusion Criteria: * RA patients will be excluded if they have a history of congestive heart failure, recurrent or active infection, a positive PPD, history of neurologic disease, Felty's syndrome, hematologic malignancy or liver disease. * RA patients will be excluded if they have a WBC count \< 4.0, Hct \< 30 or liver profile abnormalities (\> 2x normal values of AST, ALT, TBili and/or APhos). * RA patients will be excluded if they have been previously treated with anti-TNFα therapy (ENBREL, infliximab or adalimumab), IL-1ra, abatacept or B and T cell depleting therapies including rituximab or alemtuzumab. Subjects who have previously received other DMARD therapies including methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, gold, penicillamine, cyclosporine A, and cyclophosphamide must not have taken one of these medications within the past 30 days prior to instituting ENBREL. * General: Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit. Subjects who have known hypersensitivity to Enbrel or any of its components or who is known to have antibodies to etanercept. Prior or concurrent cyclophosphamide therapy. Concurrent sulfasalazine therapy. Known HIV-positive, mycobacterial disease, active severe infections, untreated Lyme disease, severe comorbidities, history of TB or TB exposure, chronic hepatitis B or hepatitis C, SLE, history of multiple sclerosis, transverse myelitis, optic neuritis or epilepsy, history of recent alcohol or substance abuse (\< 1 year), pregnant or lactating females and/or use of a live vaccine 90 days prior to, or during this study.