A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease
Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.
Authors
- Charlotte Rich‐Griffin (ORCID: https://orcid.org/0000-0001-8212-9542)
- Michael B. Brenner (ORCID: https://orcid.org/0000-0001-6202-8445)
- Jason D. Turner (ORCID: https://orcid.org/0000-0002-5423-5302)
- Brian D. Marsden (ORCID: https://orcid.org/0000-0002-1937-4091)
- Noah Spies (ORCID: https://orcid.org/0000-0002-6759-9842)
- Ruth Kulicke
- Fiona Powrie (ORCID: https://orcid.org/0000-0003-3312-5929)
- Maria Kiourlappou (ORCID: https://orcid.org/0000-0003-1792-9206)
- Luke Jostins-Dean (ORCID: https://orcid.org/0000-0002-2475-3969)
- Paul Klenerman (ORCID: https://orcid.org/0000-0003-4307-9161)
- Ashwin Jainarayanan (ORCID: https://orcid.org/0000-0003-3523-1477)
- Ruchi Tandon (ORCID: https://orcid.org/0000-0001-6438-7003)
- Stephen Taylor (ORCID: https://orcid.org/0000-0002-3559-4334)
- Dharshan Sathananthan (ORCID: https://orcid.org/0000-0002-1357-0235)
- Lisa Gartner (ORCID: https://orcid.org/0000-0002-3273-651X)
- Matthias Friedrich (ORCID: https://orcid.org/0000-0002-7551-4853)
- Calliope Athena Dendrou (ORCID: https://orcid.org/0000-0003-1179-4021)
- Carl Lee (ORCID: https://orcid.org/0000-0002-6776-2793)
- Anna Jonsson (ORCID: https://orcid.org/0000-0003-1252-8673)
- Andrew D. Filer (ORCID: https://orcid.org/0000-0001-8164-6249)
- Mark Coles (ORCID: https://orcid.org/0000-0001-8079-9358)
- Fadi Issa (ORCID: https://orcid.org/0000-0002-8279-7732)
- Nicholas E. Ilott (ORCID: https://orcid.org/0000-0002-8432-8622)
- Raphael Sanches Peres (ORCID: https://orcid.org/0000-0002-0417-779X)
- Eloise Nee
- Ray Pagliarini
- Joanna Hester (ORCID: https://orcid.org/0000-0002-7466-3849)
- Christopher Dominic Buckley (ORCID: https://orcid.org/0000-0001-6924-6402)
- Dominik Aschenbrenner (ORCID: https://orcid.org/0000-0001-7580-2567)
- Fan Zhang (ORCID: https://orcid.org/0000-0002-6102-2970)
- Danielle Ramsdell
- Aniko Rendek
- Nicolas Stransky (ORCID: https://orcid.org/0000-0002-2778-4293)
- Holm H. Uhlig (ORCID: https://orcid.org/0000-0002-6111-7355)
- Mathilde Pohin (ORCID: https://orcid.org/0000-0003-2809-9498)
- Tom R Thomas (ORCID: https://orcid.org/0000-0002-2188-3784)
- Jonas Mackerodt
- Simon P.L. Travis (ORCID: https://orcid.org/0000-0002-2690-4361)
- Peter Todd
- Saba Nayar (ORCID: https://orcid.org/0000-0002-4350-110X)
- Soumya Raychaudhuri (ORCID: https://orcid.org/0000-0002-1901-8265)
- Jacqueline H. Y. Siu (ORCID: https://orcid.org/0000-0001-5181-407X)
- Piotr Bielecki (ORCID: https://orcid.org/0000-0002-5609-1066)
- Devika Agarwal (ORCID: https://orcid.org/0000-0002-5203-307X)
- Dylan Kotliar (ORCID: https://orcid.org/0000-0002-7968-645X)
- Alexandru-Ioan Voda (ORCID: https://orcid.org/0000-0003-2974-6992)
- Alissa J. Walsh (ORCID: https://orcid.org/0000-0002-8994-1186)
- Allon Wagner (ORCID: https://orcid.org/0000-0001-5095-6009)
- Julia Pakpoor
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Centre for Human Genetics (GB)
- University College London Hospitals NHS Foundation Trust (GB)
- Lyell McEwin Hospital (AU)
- John Radcliffe Hospital (GB)
- National Institute for Health and Care Research (GB)
- University of Oxford (GB)
- Kennedy Center (DK)
- Celsius Therapeutics (United States) (US)
- Oxford BioMedica (United Kingdom) (GB)
- Oxford University Hospitals NHS Trust (GB)
- NIHR Birmingham Biomedical Research Centre (GB)
- University College London (GB)
- University of Colorado Anschutz Medical Campus (US)
- The University of Adelaide (AU)
- University of Birmingham (GB)
- University of California, Berkeley (US)
Publication Details
- Journal
- Nature Immunology
- Published
- 2024-10-22
- DOI
- https://doi.org/10.1038/s41590-024-01994-8
- Citations
- 61
- Primary Topic
- Inflammatory Bowel Disease
- Type
- article
- Field-Weighted Citation Impact
- 33.02
Funders
- Medical Research Council