a biospecimen collection study to identify the targets of disease-reactive t cells in patients with autoimmune disease

Conditions: Autoimmune Diseases; Ulcerative Colitis; Multiple Sclerosis; Scleroderma; Ankylosing Spondylitis; Celiac Disease; Non-radiographic Axial Spondyloarthritis (nr-axSpA); Crohn&amp;#39;s Disease; Birdshot Chorioretinitis

Summary: 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.

Keywords: autoimmune diseases multiple sclerosis systemic sclerosis ankylosing spondylitis scleroderma inflammatory bowel disease crohn&amp;#39;s disease non-radiographic axial spondyloarthritis (nr-axspa) birdshot chorioretinitis