Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

Bana Jabri; Dustin Shaw; Raúl Aguirre-Gamboa; Marcos Vieira; Saideep Gona; Nicholas DiNardi; Anni Wang; Anne Dumaine; Jody Gelderloos; Zachary Earley; Katherine Meckel; Cezary Ciszewski; Anabella Castillo; Kelly Monroe; Joana Torres; Shailja Shah; Jean-Frederic Colombel; Steven Itzkowitz; Rodney Newberry; Russell Cohen; David Rubin; Sarah Cobey; Iris H. Jonkers; Christopher Weber; Joel Pekow; Patrick Wilson; Luis Barreiro

doi:10.21203/rs.3.rs-1697242

Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

Bana Jabri, Dustin Shaw, Raúl Aguirre-Gamboa, Marcos Vieira, Saideep Gona, Nicholas DiNardi, Anni Wang, Anne Dumaine, Jody Gelderloos, Zachary Earley, Katherine Meckel, Cezary Ciszewski, Anabella Castillo, Kelly Monroe, Joana Torres, Shailja Shah, Jean-Frederic Colombel, Steven Itzkowitz, Rodney Newberry, Russell CohenDavid Rubin, Sarah Cobey, Iris H. Jonkers, Christopher Weber, Joel Pekow, Patrick Wilson, Luis Barreiro

Research output: Working paper › Preprint

Abstract

Primary sclerosing cholangitis (PSC) is an autoimmune-like disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with both PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single cell transcriptomics, and T- and B-cell receptor repertoire analysis of right colon tissue from PSC, IBD, and healthy controls we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia specifically in patients with PSC. This inflammatory signature is characterized by antigen-driven IL-17A+ Foxp3+ CD4 T-cell and IgG-secreting B-cell responses. These data suggest that the mechanisms of PSC and IBD dysplasia are distinct and provide molecular insights to guide prevention of colorectal cancer in PSC.

Original language	English
Publisher	Research Square
Number of pages	57
DOIs	https://doi.org/10.21203/rs.3.rs-1697242
Publication status	Published - 2022
Externally published	Yes

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1 Article

Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis
Shaw, D. G., Aguirre-Gamboa, R., Vieira, M. C., Gona, S., DiNardi, N., Wang, A., Dumaine, A., Gelderloos-Arends, J., Earley, Z. M., Meckel, K. R., Ciszewski, C., Castillo, A., Monroe, K., Torres, J., Shah, S. C., Colombel, J. F., Itzkowitz, S., Newberry, R., Cohen, R. D. & Rubin, D. T. & 8 others, Quince, C., Cobey, S., Jonkers, I. H., Weber, C. R., Pekow, J., Wilson, P. C., Barreiro, L. B. & Jabri, B., Jun 2023, In: Nature Medicine. 29, 6, p. 1520-1529 10 p.
Research output: Contribution to journal › Article › peer-review

Open Access
13 Citations (Scopus)

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Jabri, B., Shaw, D., Aguirre-Gamboa, R., Vieira, M., Gona, S., DiNardi, N., Wang, A., Dumaine, A., Gelderloos, J., Earley, Z., Meckel, K., Ciszewski, C., Castillo, A., Monroe, K., Torres, J., Shah, S., Colombel, J.-F., Itzkowitz, S., Newberry, R., ... Barreiro, L. (2022). Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis. Research Square. https://doi.org/10.21203/rs.3.rs-1697242

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title = "Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis",

abstract = "Primary sclerosing cholangitis (PSC) is an autoimmune-like disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90\% of cases. Colorectal cancer is a major complication of patients with both PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single cell transcriptomics, and T- and B-cell receptor repertoire analysis of right colon tissue from PSC, IBD, and healthy controls we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia specifically in patients with PSC. This inflammatory signature is characterized by antigen-driven IL-17A+ Foxp3+ CD4 T-cell and IgG-secreting B-cell responses. These data suggest that the mechanisms of PSC and IBD dysplasia are distinct and provide molecular insights to guide prevention of colorectal cancer in PSC.",

author = "Bana Jabri and Dustin Shaw and Ra{\'u}l Aguirre-Gamboa and Marcos Vieira and Saideep Gona and Nicholas DiNardi and Anni Wang and Anne Dumaine and Jody Gelderloos and Zachary Earley and Katherine Meckel and Cezary Ciszewski and Anabella Castillo and Kelly Monroe and Joana Torres and Shailja Shah and Jean-Frederic Colombel and Steven Itzkowitz and Rodney Newberry and Russell Cohen and David Rubin and Sarah Cobey and Jonkers, \{Iris H.\} and Christopher Weber and Joel Pekow and Patrick Wilson and Luis Barreiro",

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doi = "10.21203/rs.3.rs-1697242",

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Jabri, B, Shaw, D, Aguirre-Gamboa, R, Vieira, M, Gona, S, DiNardi, N, Wang, A, Dumaine, A, Gelderloos, J, Earley, Z, Meckel, K, Ciszewski, C, Castillo, A, Monroe, K, Torres, J, Shah, S, Colombel, J-F, Itzkowitz, S, Newberry, R, Cohen, R, Rubin, D, Cobey, S, Jonkers, IH, Weber, C, Pekow, J, Wilson, P & Barreiro, L 2022 'Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis' Research Square. https://doi.org/10.21203/rs.3.rs-1697242

TY - UNPB

T1 - Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

AU - Jabri, Bana

AU - Shaw, Dustin

AU - Aguirre-Gamboa, Raúl

AU - Vieira, Marcos

AU - Gona, Saideep

AU - DiNardi, Nicholas

AU - Wang, Anni

AU - Dumaine, Anne

AU - Gelderloos, Jody

AU - Earley, Zachary

AU - Meckel, Katherine

AU - Ciszewski, Cezary

AU - Castillo, Anabella

AU - Monroe, Kelly

AU - Torres, Joana

AU - Shah, Shailja

AU - Colombel, Jean-Frederic

AU - Itzkowitz, Steven

AU - Newberry, Rodney

AU - Cohen, Russell

AU - Rubin, David

AU - Cobey, Sarah

AU - Jonkers, Iris H.

AU - Weber, Christopher

AU - Pekow, Joel

AU - Wilson, Patrick

AU - Barreiro, Luis

PY - 2022

Y1 - 2022

N2 - Primary sclerosing cholangitis (PSC) is an autoimmune-like disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with both PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single cell transcriptomics, and T- and B-cell receptor repertoire analysis of right colon tissue from PSC, IBD, and healthy controls we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia specifically in patients with PSC. This inflammatory signature is characterized by antigen-driven IL-17A+ Foxp3+ CD4 T-cell and IgG-secreting B-cell responses. These data suggest that the mechanisms of PSC and IBD dysplasia are distinct and provide molecular insights to guide prevention of colorectal cancer in PSC.

AB - Primary sclerosing cholangitis (PSC) is an autoimmune-like disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with both PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single cell transcriptomics, and T- and B-cell receptor repertoire analysis of right colon tissue from PSC, IBD, and healthy controls we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia specifically in patients with PSC. This inflammatory signature is characterized by antigen-driven IL-17A+ Foxp3+ CD4 T-cell and IgG-secreting B-cell responses. These data suggest that the mechanisms of PSC and IBD dysplasia are distinct and provide molecular insights to guide prevention of colorectal cancer in PSC.

U2 - 10.21203/rs.3.rs-1697242

DO - 10.21203/rs.3.rs-1697242

M3 - Preprint

BT - Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

PB - Research Square

ER -

Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

Abstract

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Research output

Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

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