A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease
Thomas, Tom Friedrich, Matthias Rich-Griffin, Charlotte Pohin, Mathilde Agarwal, Devika Pakpoor, Julia Lee, Carl Tandon, Ruchi Rendek, Aniko Aschenbrenner, Dominik
Thomas, Tom
Friedrich, Matthias
Rich-Griffin, Charlotte
Pohin, Mathilde
Agarwal, Devika
Pakpoor, Julia
Lee, Carl
Tandon, Ruchi
Rendek, Aniko
Aschenbrenner, Dominik
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2024-10-22
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Abstract
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.
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Thomas T, Friedrich M, Rich-Griffin C, Pohin M, Agarwal D, Pakpoor J, Lee C, Tandon R, Rendek A, Aschenbrenner D, Jainarayanan A, Voda A, Siu JHY, Sanches-Peres R, Nee E, Sathananthan D, Kotliar D, Todd P, Kiourlappou M, Gartner L, Ilott N, Issa F, Hester J, Turner J, Nayar S, Mackerodt J, Zhang F, Jonsson A, Brenner M, Raychaudhuri S, Kulicke R, Ramsdell D, Stransky N, Pagliarini R, Bielecki P, Spies N, Marsden B, Taylor S, Wagner A, Klenerman P, Walsh A, Coles M, Jostins-Dean L, Powrie FM, Filer A, Travis S, Uhlig HH, Dendrou CA, Buckley CD. A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease. Nat Immunol. 2024 Nov;25(11):2152-2165. doi: 10.1038/s41590-024-01994-8. Epub 2024 Oct 22.
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