Identifying and Characterizing Preclinical MS

The purpose of this study is to try and learn how to identify multiple sclerosis (MS) before it causes any neurologic symptoms. By the time MS causes symptoms, the disease has often been causing damage under the surface for years. Because early treatment of MS helps prevent long term disability from the disease, the investigators are hypothesizing that if MS could be detected (and treated) before symptoms start, the disease might be preventable.

The investigators believe that people who go on to develop MS have changes in their immune systems long before they have symptoms. Some of these changes might be in "hidden" parts of the body, like lymph nodes or fat tissue. The investigators want to study people who have risk factors for MS to try and learn to detect very early signs of disease.

Study procedures will include:

All study participants will undergo a blood draw and an oral swab; they will also complete baseline questionnaires All study participants will be contacted approximately once per year and asked to complete some additional questionnaires All study participants may be asked to donate repeat blood/oral swab specimens or stool specimens over time on an ad hoc basis Study participants who agree will undergo additional optional procedures to study the immune system in different parts of the body.

The optional procedures include:

Lumbar punctures (to obtain spinal fluid) Tonsil biopsy Fat biopsy (to obtain fat cells) Lymph node biopsy (to obtain lymph node tissues with immune cells) Traditional brain MRI Low-field (portable) brain MRI

One in-person visit is required. There will also be annual phone/email contact, which may take up to 30 minutes The required in-person visit will take approximately 1 hour total. Anyone who agrees to donate follow up biospecimens, undergo a procedure, or undergo an MRI will have additional in-person visits Optional visits for donating biospecimens, having a procedure or getting an MRI may take longer (up to 3 hours), depending on what is happening during the visit.