This study is to address the mechanism of action of teriflunomide in a phase IV open label trial with Teriflunomide in multiple sclerosis. Researchers will recruit 20 relapsing remitting multiple sclerosis patients (Group 1) start on treatment with teriflunomide (Aubagio). Patients will be enrolled from the Multiple Sclerosis Center at the University of Michigan Health System in Ann Arbor. Meanwhile, 10 healthy controls will be recruited, to establish a healthy baseline for B and T cells, which are affected by both MS and its treatment (Group 2). This Study will collect baseline pre-treatment blood samples periodically for up to 2 years. Blood biomarker changes will be correlated with clinical response to teriflunomide treatment intervention.

Multiple sclerosis is the most common autoimmune inflammatory and debilitating chronic demyelinating disease of the central nervous system mainly affecting young adults. There is a tremendous need to understand the mechanism of action of the treatment and how they might work in multiple sclerosis patients. Most recently, teriflunomide (AubagioTM) has been demonstrated to act as an immune modulatory therapy for patients with multiple sclerosis. Although one biochemical mechanism of action is understood to be related to inhibition of dihydroorotate dehydrogenase (DHODH) which affects synthesis of pyrimidine nucleotides, there have also been reports that the functions of regulatory T cells are promoted by these drugs independent of DHODH. Much accumulating evidence suggests that specialized subsets of B lymphocytes are important inducers of regulatory T cells, as well as having killer functions that may preferentially target TH1 and TH17 cells.

This study aims to address the mechanism of action of teriflunomide in a phase IV open label trial with Teriflunomide in multiple sclerosis

Inclusion Criteria:

1. Patients with clinically-defined relapsing-remitting MS (RRMS) who " are newly starting on teriflunomide (AubagioTM) at the time of enrollment " have no evidence of relapse or corticosteroid treatment use within 2 months prior to enrollment

   OR

   Healthy controls who do not have a significant medical condition such as cancer, chronic infection, or autoimmune disease, have not taken steroids in the past 2 months, and who are not on an immune suppressant medication.

2. Ability to give informed consent

3. Willing to have blood drawn as scheduled in the protocol

4. Willing and able to complete all procedures and evaluations related to the study

Exclusion Criteria:

1. Medical or psychiatric conditions that may affect the patient's ability to give informed consent

2. Has received an experimental drug within 30 days of enrollment

3. Concomitant other disease modifying medications (such as Rebif, Betaseron, Avonex, Copaxone, Gilenya, Tecfidera, Alemtuzumab, methotrexate, azathioprine, mitoxantrone, cyclophosphamide, cyclosporine, natalizumab, rituxan, ocrelizumab, etc.) without the minimal washout period stated below:

   " rebif, betaseron, avonex, copaxone within 1 month " zinbryta, plegridy, gilenya, tecfidera within 2 months " natalizumab within 3 months " immunosuppressive/chemotherapeutic medications (e.g. azathioprine, methotrexate) within 6 months " cyclophosphamide within 1 year " rituximab, ofatumumab, ocrelizumab, cladribine within 1 year " alemtuzumab at any time " any mitoxantrone during previous 2 years prior to randomization or evidence of cardiotoxicity following mitoxantrone or a cumulative life-time dose of more than 60 mg/m2 " lymphoid irradiation, bone marrow transplantation or other immunosuppressive treatments with effects potentially lasting over 6 months, at any time

4. Has any contraindication to high-dose immunotherapy, including pregnancy, trying to become pregnant, or breast feeding during the study.

A total of 20 multiple sclerosis (MS) patients and 10 healthy controls will be recruited to voluntarily donate blood for the study. Blood samples will be collected prior to starting teriflunomide treatment (baseline) and after 3, 6, 9, 12, 18 and 24 months of treatment (+/- 2 weeks).