Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn’s Disease
Background and Aims: Management of Crohn’s disease (CD) requires frequent monitoring for disease activity and response to therapy. In this study, we examined the clinical utility of a novel stool-derived eukaryotic RNA (seRNA)-based diagnostic in patients with CD. Methods: Stool samples were collect...
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Elsevier
2024-01-01
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| Series: | Gastro Hep Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772572324001079 |
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| author | Ryan B. Ghannam Erica K. Barnell Ali Osman Richard Roberts Patrick Donohue Spencer King Jack Land Clayton Grass Matthew A. Ciorba Parakkal Deepak |
| author_facet | Ryan B. Ghannam Erica K. Barnell Ali Osman Richard Roberts Patrick Donohue Spencer King Jack Land Clayton Grass Matthew A. Ciorba Parakkal Deepak |
| author_sort | Ryan B. Ghannam |
| collection | DOAJ |
| description | Background and Aims: Management of Crohn’s disease (CD) requires frequent monitoring for disease activity and response to therapy. In this study, we examined the clinical utility of a novel stool-derived eukaryotic RNA (seRNA)-based diagnostic in patients with CD. Methods: Stool samples were collected from 68 individuals for up to 3 time points prior to, and after initiation of an advanced therapy. Stool samples underwent RNA extraction and sequencing using a custom capture panel (n = 1507 transcripts). seRNA signatures were compared to Crohn's Disease Activity Index scores and endoscopies, when available. Random forest models classified disease severity when compared to Crohn's Disease Activity Index scores. seRNA signatures were also used to assess expression of the therapy target and cell type abundance at various time points. Results: Across all 102 samples collected from 68 individuals, the classifier successfully parsed individuals with active disease (n = 37) relative to those in remission (n = 65) with 87% sensitivity and 77% specificity, respectively. A second classifier, which was employed on subjects with active disease (n = 37), successfully parsed individuals with mild disease (n = 15) from those with moderate disease (n = 22) with 93% and 86% sensitivity, respectively. For the 16 subjects with longitudinal data, seRNA expression of the therapeutic target (eg, ITGA4/ITGB7 for vedolizumab or IL12/IL23 for ustekinumab) as well as lymphocyte burden was correlated with response. Conclusion: A novel seRNA and informatic-based method reliably discriminates active disease from remission and stratifies mild from moderate CD activity. This demonstrates preliminary feasibility to predict therapeutic response and assess disease activity for patients with CD. |
| format | Article |
| id | doaj-art-9e40a1ed1b6c433b9ed17e6bd0382c1b |
| institution | Kabale University |
| issn | 2772-5723 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Gastro Hep Advances |
| spelling | doaj-art-9e40a1ed1b6c433b9ed17e6bd0382c1b2024-11-29T06:26:23ZengElsevierGastro Hep Advances2772-57232024-01-013810791086Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn’s DiseaseRyan B. Ghannam0Erica K. Barnell1Ali Osman2Richard Roberts3Patrick Donohue4Spencer King5Jack Land6Clayton Grass7Matthew A. Ciorba8Parakkal Deepak9Department of Research and Development, Geneoscopy, Saint Louis, MissouriDepartment of Research and Development, Geneoscopy, Saint Louis, Missouri; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Correspondence: Address correspondence to: Erica K. Barnell, MD, PhD, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, Missouri 63110.Division of Gastroenterology, Inflammatory Bowel Diseases Center, Washington University School of Medicine, St. Louis, Missouri; Division of Hospital Medicine, Washington University School of Medicine, St. Louis, MissouriDepartment of Research and Development, Geneoscopy, Saint Louis, MissouriDepartment of Medicine, Washington University School of Medicine, St. Louis, MissouriDepartment of Research and Development, Geneoscopy, Saint Louis, MissouriDepartment of Research and Development, Geneoscopy, Saint Louis, MissouriDepartment of Research and Development, Geneoscopy, Saint Louis, MissouriDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri; Division of Gastroenterology, Inflammatory Bowel Diseases Center, Washington University School of Medicine, St. Louis, MissouriDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri; Division of Gastroenterology, Inflammatory Bowel Diseases Center, Washington University School of Medicine, St. Louis, MissouriBackground and Aims: Management of Crohn’s disease (CD) requires frequent monitoring for disease activity and response to therapy. In this study, we examined the clinical utility of a novel stool-derived eukaryotic RNA (seRNA)-based diagnostic in patients with CD. Methods: Stool samples were collected from 68 individuals for up to 3 time points prior to, and after initiation of an advanced therapy. Stool samples underwent RNA extraction and sequencing using a custom capture panel (n = 1507 transcripts). seRNA signatures were compared to Crohn's Disease Activity Index scores and endoscopies, when available. Random forest models classified disease severity when compared to Crohn's Disease Activity Index scores. seRNA signatures were also used to assess expression of the therapy target and cell type abundance at various time points. Results: Across all 102 samples collected from 68 individuals, the classifier successfully parsed individuals with active disease (n = 37) relative to those in remission (n = 65) with 87% sensitivity and 77% specificity, respectively. A second classifier, which was employed on subjects with active disease (n = 37), successfully parsed individuals with mild disease (n = 15) from those with moderate disease (n = 22) with 93% and 86% sensitivity, respectively. For the 16 subjects with longitudinal data, seRNA expression of the therapeutic target (eg, ITGA4/ITGB7 for vedolizumab or IL12/IL23 for ustekinumab) as well as lymphocyte burden was correlated with response. Conclusion: A novel seRNA and informatic-based method reliably discriminates active disease from remission and stratifies mild from moderate CD activity. This demonstrates preliminary feasibility to predict therapeutic response and assess disease activity for patients with CD.http://www.sciencedirect.com/science/article/pii/S2772572324001079Crohn’s DiseaseNoninvasive DiagnosticsStool Eukaryotic RNADisease Activity and Therapeutic Response |
| spellingShingle | Ryan B. Ghannam Erica K. Barnell Ali Osman Richard Roberts Patrick Donohue Spencer King Jack Land Clayton Grass Matthew A. Ciorba Parakkal Deepak Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn’s Disease Gastro Hep Advances Crohn’s Disease Noninvasive Diagnostics Stool Eukaryotic RNA Disease Activity and Therapeutic Response |
| title | Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn’s Disease |
| title_full | Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn’s Disease |
| title_fullStr | Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn’s Disease |
| title_full_unstemmed | Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn’s Disease |
| title_short | Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn’s Disease |
| title_sort | noninvasive stool rna test approximates disease activity in patients with crohn s disease |
| topic | Crohn’s Disease Noninvasive Diagnostics Stool Eukaryotic RNA Disease Activity and Therapeutic Response |
| url | http://www.sciencedirect.com/science/article/pii/S2772572324001079 |
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