The most clinically meaningful way to discover new targets of T cells in autoimmune diseases is to study the tissues of patients with active autoimmune disease mediated organ inflammation. These tissues contain both cytotoxic and helper T cells that are driving their disease, and these T cells are being guided by TCRs that recognize tissue-specific targets. By collecting tissue when a patient has active inflammation, it is possible to determine which T cells are activated and undergoing clonal expansion in the patient's diseased organ. TScan has developed a genome-wide, high-throughput technology to determine the natural, physiological target of any TCR (Kula, 2019). The goal of this study is to isolate T cells from inflamed tissues and matched blood samples and/or matched normal tissues (for patients with inflammatory bowel diseases). T cell clones that are expanded in diseased tissues relative to blood or normal tissues will be selected and the targets of their TCRs will be defined using TScan's genome-wide, high-throughput target ID technology.
The goal of this study is to discover a collection of peptide targets, along with their associated TCRs to be developed as new tolerogenic therapies for patients with autoimmune diseases.
Inflammatory Bowel Diseases - Crohn's Disease or ulcerative colitis
Celiac disease
Ankylosing spondylitis or Non radiographic axial spondyloarthritis (nr-axSpA)
Multiple sclerosis
Glucocorticoids including prednisone, methylprednisolone (Solu-medrol), budesonide (Entocort), hydrocortisone (Solu-cortef), dexamethasone (Decadron), betamethasone (Betaject)
Sulfasalazine (Azulfidine)
Aminosalicylates including mesalamine/ mesalazine (Asacol, Pentasa).
Thiopurines including azathioprine (Imuran) and 6-mercaptopurine (Purixan)
Patients with a known or suspected autoimmune disease will be enrolled into the study. Additionally, patients who have an apparent evolving autoimmune disease may be eligible. Patients with autoimmune disease who had excess materials cryopreserved in a manner that is expected to yield sufficient T cells for this research study, and where biologic samples were ethically obtained, will be utilized for this study. Both men and women and members of all races and ethnic groups are eligible for this protocol. It is expected that the mix of patients entering this study will reflect the demographics of the clinic population seen in hospitals and associated clinics in the region from which the biologic materials are collected.
Case-only
Prospective
Companion blood samples with procedure
Procedure/SurgeryParticipants in all cohorts will have a companion blood sample obtained on or around the time of the procedure intended to obtain tissue or fluid.
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Treatment groupsSee each treatment group below.
Identify peptide targets together with their associated TCRs in patients with autoimmune diseases under study.
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