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Biopsy and blood-based molecular biomarker of inflammation in IBD.
Argmann, Carmen; Hou, Ruixue; Ungaro, Ryan C; Irizar, Haritz; Al-Taie, Zainab; Huang, Ruiqi; Kosoy, Roman; Venkat, Swati; Song, Won-Min; Di'Narzo, Antonio F; Losic, Bojan; Hao, Ke; Peters, Lauren; Comella, Phillip H; Wei, Gabrielle; Atreja, Ashish; Mahajan, Milind; Iuga, Alina; Desai, Prerak T; Branigan, Patrick; Stojmirovic, Aleksandar; Perrigoue, Jacqueline; Brodmerkel, Carrie; Curran, Mark; Friedman, Joshua R; Hart, Amy; Lamousé-Smith, Esi; Wehkamp, Jan; Mehandru, Saurabh; Schadt, Eric E; Sands, Bruce E; Dubinsky, Marla C; Colombel, Jean-Frederic; Kasarskis, Andrew; Suárez-Fariñas, Mayte.
Afiliação
  • Argmann C; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA carmen.argmann@mssm.edu mayte.suarezfarinas@mssm.edu.
  • Hou R; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Ungaro RC; The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Irizar H; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Al-Taie Z; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Huang R; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Kosoy R; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Venkat S; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Song WM; Janssen R&D, Spring House, Pennsylvania, USA.
  • Di'Narzo AF; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Losic B; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Hao K; Sema4, Stamford, Connecticut, USA.
  • Peters L; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Comella PH; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Wei G; Sema4, Stamford, Connecticut, USA.
  • Atreja A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Mahajan M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Iuga A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Desai PT; The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Branigan P; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Stojmirovic A; Sema4, Stamford, Connecticut, USA.
  • Perrigoue J; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Brodmerkel C; Janssen R&D, Spring House, Pennsylvania, USA.
  • Curran M; Janssen R&D, Spring House, Pennsylvania, USA.
  • Friedman JR; Janssen R&D, Spring House, Pennsylvania, USA.
  • Hart A; Janssen R&D, Spring House, Pennsylvania, USA.
  • Lamousé-Smith E; Janssen R&D, Spring House, Pennsylvania, USA.
  • Wehkamp J; Janssen R&D, Spring House, Pennsylvania, USA.
  • Mehandru S; Janssen R&D, Spring House, Pennsylvania, USA.
  • Schadt EE; Janssen R&D, Spring House, Pennsylvania, USA.
  • Sands BE; Janssen R&D, Spring House, Pennsylvania, USA.
  • Dubinsky MC; Janssen R&D, Spring House, Pennsylvania, USA.
  • Colombel JF; The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Kasarskis A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Suárez-Fariñas M; Sema4, Stamford, Connecticut, USA.
Gut ; 72(7): 1271-1287, 2023 07.
Article em En | MEDLINE | ID: mdl-36109152
ABSTRACT

OBJECTIVE:

IBD therapies and treatments are evolving to deeper levels of remission. Molecular measures of disease may augment current endpoints including the potential for less invasive assessments.

DESIGN:

Transcriptome analysis on 712 endoscopically defined inflamed (Inf) and 1778 non-inflamed (Non-Inf) intestinal biopsies (n=498 Crohn's disease, n=421 UC and 243 controls) in the Mount Sinai Crohn's and Colitis Registry were used to identify genes differentially expressed between Inf and Non-Inf biopsies and to generate a molecular inflammation score (bMIS) via gene set variance analysis. A circulating MIS (cirMIS) score, reflecting intestinal molecular inflammation, was generated using blood transcriptome data. bMIS/cirMIS was validated as indicators of intestinal inflammation in four independent IBD cohorts.

RESULTS:

bMIS/cirMIS was strongly associated with clinical, endoscopic and histological disease activity indices. Patients with the same histologic score of inflammation had variable bMIS scores, indicating that bMIS describes a deeper range of inflammation. In available clinical trial data sets, both scores were responsive to IBD treatment. Despite similar baseline endoscopic and histologic activity, UC patients with lower baseline bMIS levels were more likely treatment responders compared with those with higher levels. Finally, among patients with UC in endoscopic and histologic remission, those with lower bMIS levels were less likely to have a disease flare over time.

CONCLUSION:

Transcriptionally based scores provide an alternative objective and deeper quantification of intestinal inflammation, which could augment current clinical assessments used for disease monitoring and have potential for predicting therapeutic response and patients at higher risk of disease flares.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colite Ulcerativa / Doença de Crohn Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Humans Idioma: En Revista: Gut Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colite Ulcerativa / Doença de Crohn Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Humans Idioma: En Revista: Gut Ano de publicação: 2023 Tipo de documento: Article