A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease

• Published in: Nature immunology Vol. 25; no. 11; pp. 2152 - 2165
• Main Authors: Thomas, Tom, Friedrich, Matthias, Rich-Griffin, Charlotte, Pohin, Mathilde, Agarwal, Devika, Pakpoor, Julia, Lee, Carl, Tandon, Ruchi, Rendek, Aniko, Aschenbrenner, Dominik, Jainarayanan, Ashwin, Voda, Alexandru, Siu, Jacqueline H. Y., Sanches-Peres, Raphael, Nee, Eloise, Sathananthan, Dharshan, Kotliar, Dylan, Todd, Peter, Kiourlappou, Maria, Gartner, Lisa, Ilott, Nicholas, Issa, Fadi, Hester, Joanna, Turner, Jason, Nayar, Saba, Mackerodt, Jonas, Zhang, Fan, Jonsson, Anna, Brenner, Michael, Raychaudhuri, Soumya, Kulicke, Ruth, Ramsdell, Danielle, Stransky, Nicolas, Pagliarini, Ray, Bielecki, Piotr, Spies, Noah, Marsden, Brian, Taylor, Stephen, Wagner, Allon, Klenerman, Paul, Walsh, Alissa, Coles, Mark, Jostins-Dean, Luke, Powrie, Fiona M., Filer, Andrew, Travis, Simon, Uhlig, Holm H., Dendrou, Calliope A., Buckley, Christopher D.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2024; Nature Publishing Group
• Subjects: 631/250/249/2510/257/1402; 692/699/249/2510/2511; Adalimumab - therapeutic use; Adult; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Biological treatment; Biomedical and Life Sciences; Biomedicine; Biopsy; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - immunology; Crohn Disease - drug therapy; Crohn Disease - immunology; Crohn's disease; Female; Granuloma; Humans; Immunology; Infectious Diseases; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - immunology; Inflammatory diseases; Interferon; Interferons - metabolism; Longitudinal Studies; Lymphocytes T; Male; Medical treatment; Monoclonal antibodies; Precision medicine; Remission; Remission (Medicine); Resource; Rheumatoid arthritis; Rheumatoid synovitis; Signal Transduction; Single-Cell Analysis; Spatial analysis; Transcriptome; Transcriptomes; Tumor necrosis factor; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumors; Ulcerative colitis
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-024-01994-8

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. In this Resource, Buckley and colleagues profile patients with Crohn’s disease and ulcerative colitis before and after adalimumab therapy. Specific pretreatment differences in the epithelial and myeloid compartments were associated with remission outcomes in both diseases. The authors also describe the cellular circuitry in nonremission patients following treatment.