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| ID | Type | Description | Link |
|---|---|---|---|
| U01AI101990 | U.S. NIH Grant/Contract | View source | |
| R01AI118855-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| Arthritis Foundation | OTHER |
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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The immune system is influenced by the commensal microbes that live in the gut and on the skin. This study aims to characterize the microbiota of subjects with autoimmune disease in order to determine whether certain microbial species may cause or worsen immune-mediated diseases
This is a combination of a defined pilot microbiome study as well as exploratory mechanistic research with candidate commensals identified based on known structures accessible in public databases. In the observational prospective two-center study, subjects will be followed for 8 weeks. The study will consist of a total of 3 study visits (0, 4 and 8 weeks). Screening and baseline visits (week 0) will take place at the same time. A study window period of +/- 7 days will be allowed for follow-up study visits. The mechanistic in vitro research with subjects' blood cells and candidate commensals will typically require between 2-4 visits for sampling, but will not be limited by the frequency of visits.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Systemic Lupus Erythematosus | Blood, stool, and swab samples will be collected at baseline, week 4, and week 8 and compared with control samples |
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| Subacute Cutaneous Lupus Erythematosus | Blood, stool, and swab samples will be collected at baseline, week 4, and week 8 and compared with control samples |
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| Control | Blood, stool, and swab samples will be collected for comparison to each disease group |
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| Cutaneous T-Cell Lymphoma | Blood and swab samples will be collected for comparison to each disease group |
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| Autoimmune Disorders | Blood, stool, and swab samples will be collected for comparison to each disease group |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sample Collection | Other | Sample collection of blood, stool, and buccal and skin swab samples will be collected at baseline, week 4, and week 8 |
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| Measure | Description | Time Frame |
|---|---|---|
| Difference in Commensal bacteria | Difference in disease group vs. control commensal bacteria will be compared by looking at the relative abundances of the microbiota | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Immune Cross-reactivity with commensal bacteria | T and B cells in patients with immune-mediated diseases will cross react with specific microbial antigens | 8 weeks |
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Inclusion Criteria:
Exclusion criteria for pilot study (subjects enrolled in the exploratory mechanistic study arm will not be required to meet exclusion criteria and may be enrolled if the investigators believe that the subject can help address the scientific aim)..
Exclusion Criteria:
Ongoing chronic infection (viral, bacterial or fungal) including known HIV, Hepatitis B/C
Acute infection receiving any antibiotics or any use of antibiotics within 90 days prior to screening
For skin swab collection (see also appendix D):
For oral swab collection (see also appendix D):
Major gastrointestinal surgery less than 5 years prior to enrollment (with the exception of appendectomy)
Any Gastrointestinal bleeding history
Inflammatory Bowel Disease diagnosed by biopsy
Bulimia or anorexia nervosa
Probiotics (greater than estimated 109 cfu or organisms per day) within 90 days prior to enrollment (with the exception of fermented beverages, milks or yogurts).
Morbid obesity (BMI ≥ 40)
Type I Diabetes Mellitus
Diabetes Mellitus type 2, poorly controlled defined as Hgb A1c greater than 8% on medical therapy
Malignancy within one year prior to screening (with the exception of non-metastatic squamous or basal cell skin carcinomas and cervical carcinoma if received curative surgical treatment)
Known illicit drug or alcohol abuse
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Subjects with immune-mediated disorders including but not limited to: systemic lupus, cutaneous lupus, Sjogren's Syndrome, mixed connective tissue disease, dermatomyositis/polymyositis, celiac sprue with or without dermatitis herpetiformis, scleroderma, ANCA-associated vasculitis
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| Name | Affiliation | Role |
|---|---|---|
| Martin Kriegel, MD, PhD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale New Haven Hospital | New Haven | Connecticut | 06519 | United States | ||
| Hospital for Special Surgery |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32457482 | Background | Ruff WE, Greiling TM, Kriegel MA. Host-microbiota interactions in immune-mediated diseases. Nat Rev Microbiol. 2020 Sep;18(9):521-538. doi: 10.1038/s41579-020-0367-2. Epub 2020 May 26. | |
| 30581114 | Result | Zegarra-Ruiz DF, El Beidaq A, Iniguez AJ, Lubrano Di Ricco M, Manfredo Vieira S, Ruff WE, Mubiru D, Fine RL, Sterpka J, Greiling TM, Dehner C, Kriegel MA. A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity. Cell Host Microbe. 2019 Jan 9;25(1):113-127.e6. doi: 10.1016/j.chom.2018.11.009. Epub 2018 Dec 20. |
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| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
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whole blood, oral swab, skin swab, stool
| New York |
| New York |
| 10021 |
| United States |
| 31227334 | Result | Ruff WE, Dehner C, Kim WJ, Pagovich O, Aguiar CL, Yu AT, Roth AS, Vieira SM, Kriegel C, Adeniyi O, Mulla MJ, Abrahams VM, Kwok WW, Nussinov R, Erkan D, Goodman AL, Kriegel MA. Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity. Cell Host Microbe. 2019 Jul 10;26(1):100-113.e8. doi: 10.1016/j.chom.2019.05.003. Epub 2019 Jun 18. |
| 29593104 | Result | Greiling TM, Dehner C, Chen X, Hughes K, Iniguez AJ, Boccitto M, Ruiz DZ, Renfroe SC, Vieira SM, Ruff WE, Sim S, Kriegel C, Glanternik J, Chen X, Girardi M, Degnan P, Costenbader KH, Goodman AL, Wolin SL, Kriegel MA. Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Sci Transl Med. 2018 Mar 28;10(434):eaan2306. doi: 10.1126/scitranslmed.aan2306. |
| 29590047 | Result | Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W, Barbieri A, Kriegel C, Mehta SS, Knight JR, Jain D, Goodman AL, Kriegel MA. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science. 2018 Mar 9;359(6380):1156-1161. doi: 10.1126/science.aar7201. |
| 39874239 | Derived | Zhou H, Balint D, Shi Q, Vartanian T, Kriegel MA, Brito I. Lupus and inflammatory bowel disease share a common set of microbiome features distinct from other autoimmune disorders. Ann Rheum Dis. 2025 Jan;84(1):93-105. doi: 10.1136/ard-2024-225829. Epub 2025 Jan 2. |