Mandeep Singh, Raymond HY Louie, Jerome Samir, Matthew Field, Claire Milthorpe Milthorpe, Thiruni Adikari, Joseph Mackie, Ellise Roper, Megan Faulks, Katherine JL Jackson, Andrew Calcino, Melinda Y Hardy, Piers Blombery, Timothy G Amos, Ira W Deveson, Scott A Read, Dmitry Shek, Antoine Guerin, Cindy S Ma, Stuart G Tangye, Antonio Di Sabatino, Marco Lenti, Alessandra Pasini, Rachele Ciccocioppo, Golo Ahlenstiel, Dan Suan, Jason A Tye-Din, Christopher C Goodnow, Fabio Luciani
{"title":"Expanded T cell clones with lymphoma driver somatic mutations in refractory celiac disease","authors":"Mandeep Singh, Raymond HY Louie, Jerome Samir, Matthew Field, Claire Milthorpe Milthorpe, Thiruni Adikari, Joseph Mackie, Ellise Roper, Megan Faulks, Katherine JL Jackson, Andrew Calcino, Melinda Y Hardy, Piers Blombery, Timothy G Amos, Ira W Deveson, Scott A Read, Dmitry Shek, Antoine Guerin, Cindy S Ma, Stuart G Tangye, Antonio Di Sabatino, Marco Lenti, Alessandra Pasini, Rachele Ciccocioppo, Golo Ahlenstiel, Dan Suan, Jason A Tye-Din, Christopher C Goodnow, Fabio Luciani","doi":"10.1101/2024.03.17.24304320","DOIUrl":null,"url":null,"abstract":"Intestinal inflammation continues in a subset of celiac disease (CD) patients despite a gluten-free diet. Here, by applying multiomic single cell analysis to duodenal biopsies, we find low-grade malignancies with lymphoma driver mutations in refractory CD type 2 (RCD2) patients comprise surface CD3 negative (sCD3-) lymphocytes stalled at an innate lymphoid cell (ILC) - progenitor T cell stage undergoing extensive TCR recombination. In people with refractory CD type 1 (RCD1), who currently lack explanation, we discover sCD3+ T cells with lymphoma driver mutations forming large clones displaying inflammatory and cytotoxic molecular profiles in 6 of 10 individuals, and a single small clone in 1 of 4 active recently diagnosed CD cases. Accumulation of driver-mutated T cells and their sCD3- progenitors may explain chronic, non-responsive autoimmunity.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv - Allergy and Immunology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.03.17.24304320","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Intestinal inflammation continues in a subset of celiac disease (CD) patients despite a gluten-free diet. Here, by applying multiomic single cell analysis to duodenal biopsies, we find low-grade malignancies with lymphoma driver mutations in refractory CD type 2 (RCD2) patients comprise surface CD3 negative (sCD3-) lymphocytes stalled at an innate lymphoid cell (ILC) - progenitor T cell stage undergoing extensive TCR recombination. In people with refractory CD type 1 (RCD1), who currently lack explanation, we discover sCD3+ T cells with lymphoma driver mutations forming large clones displaying inflammatory and cytotoxic molecular profiles in 6 of 10 individuals, and a single small clone in 1 of 4 active recently diagnosed CD cases. Accumulation of driver-mutated T cells and their sCD3- progenitors may explain chronic, non-responsive autoimmunity.
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