A Biospecimen Collection Study to Identify the Targets of Disease-Reactive T Cells in Patients with Autoimmune Disease

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.


Eligibility Criteria:
Cohort Legend: Cohort 1: Inflammatory Bowel Diseases - Crohn's Disease or Ulcerative Colitis, Cohort 2: Celiac Disease, Cohort 3: Ankylosing spondylitis or non-radiographic axial spondyloarthritis (nr-axSpA), Cohort 4: Multiple Sclerosis, Cohort 5: Scleroderma, Cohort 6: Systemic Sclerosis with pulmonary involvement, Cohort 7: Other Autoimmune Disease, Cohort 8: Apparent Evolving Autoimmune Disease, Cohort 9: Frozen Cryopreserved

Inclusion Criteria:

* Study cohorts 1,2,3,4,5,6,7,8.9: Known or suspected diagnosis, with subsequent diagnostic confirmation, of one of the following cohorts associated with the following autoimmune diseases:
* Inflammatory Bowel Diseases - Crohn's Disease or ulcerative colitis
* Celiac disease
* Ankylosing spondylitis or Non radiographic axial spondyloarthritis (nr-axSpA)
* Multiple sclerosis
* Scleroderma
* Systemic sclerosis with pulmonary involvement
* Other autoimmune disease (as agreed between Investigator and Sponsor)
* Apparent evolving autoimmune disease
* Frozen cryopreserved
* Age equal or greater than 18 years at time of informed consent.
* Ability to understand and willingness to sign an informed consent document when informed consent is required by an ethical review board.
* On disease-modifying treatments that are not known to be directly T cell toxic.

Such treatments are allowed and include:

* Non-steroidal anti-inflammatory drugs including aspirin, ibuprofen, acetaminophen, celecoxib, indomethacin, diclofenac, etodolac, naproxen, meloxicam, sulindac, nabumetone amongst others.
* Tumor necrosis factor alpha (TNF-alpha) antagonists including infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi) and biosimilar drugs with the same generic name.
* Interleukin-12/23 antagonists including ustekinumab (Stelara) and risankizumab-rzaa (Skyrizi)
* Alpha-4-integrin antagonists including vedolizumab (Entyvio), natalizumab (Tysabri)
* Interleukin-17 inhibitors including secukinumab (Cosentyx), ixekizumab (Taltz)
* Recombinant interferon beta
* CD20 antagonists including rituximab (Rituxan), ocrelizumab (Ocrevus), ofatumumab (Kesimpta)
* Oral fumarates including dimethyl fumarate (Tecfidera), diroximel fumarate (Vumerity), monomethyl fumarate (Bafiertam)
* Oral sphingosine 1-phosphate receptor (S1PR) modulators including fingolimod (Gilenya), siponimod (Mayzent), ozanimod (Zeposia), ponesimod (Ponvory)
* Oral glatiramer acetate (copolymer 1; Copaxone)
* Patient is an appropriate candidate for a procedure to obtain a biopsy, tissue samples or biologic materials during a clinically indicated procedure where it is expected that excess materials could be used for research OR
* In the opinion of the clinical investigator, a patient is an appropriate, low-risk candidate for a research only procedure to obtain a biopsy, tissue samples or biologic materials.

Exclusion Criteria:

* On treatment with drugs that are known to be T cell toxic and cannot be held for at least 4 weeks or longer. The following treatments are not allowed except in designated cohorts when approved by Sponsor:
* 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)
* Systemic JAK inhibitors including tofacitinib (Xeljanz), abrocitinib (Cibinqo), baricitinib (Olumiant), upadacitinib (Rinvoq)
* CD52 inhibitors including alemtuzumab (Campath)
* Methotrexate
* Cladribine
* Teriflunomide (Aubagio)
* Concurrent disease or condition that would make the patient inappropriate for study participation, or any serious medical or psychiatric disorder that would interfere with the subject's safety.
* Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
* Patients receiving research biopsy procedures will not have a history of serious or life-threatening allergic reaction to local anesthetics (i.e., lidocaine, xylocaine), if local anesthetic is required for the procedure or to medications used for sedation during a procedure.
* Pregnant or nursing women are excluded because there may be unanticipated adverse events and increased risk to both mother and fetus in the setting of local anesthetic or study procedures.
* Any other medical or psychiatric condition, which in the opinion of the patient's treating clinician, would make participation in this protocol unreasonably hazardous for the patient.