Expanded T cell clones with lymphoma driver somatic mutations in refractory celiac disease
Singh, M.; Louie, R. H.; Samir, J.; Field, M.; Milthorpe, C. M.; Adikari, T.; Mackie, J.; Roper, E.; Faulks, M.; Jackson, K. J.; Calcino, A.; Hardy, M. Y.; Blombery, P.; Amos, T. G.; Deveson, I. W.; Read, S. A.; Shek, D.; Guerin, A.; Ma, C. S.; Tangye, S. G.; Di Sabatino, A.; Lenti, M.; Pasini, A.; Ciccocioppo, R.; Ahlenstiel, G.; Suan, D.; Tye-Din, J. A.; Goodnow, C. C.; Luciani, F.
Show 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. One-Sentence SummaryTreatment refractory autoimmunity in celiac disease may be explained by dysregulated T cells and progenitors that have acquired lymphoma-driver mutations.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions 96%
- Cross-tissue immune cell analysis reveals tissue-specific adaptations and clonal architecture across the human body 96%
- A cell atlas of human thymic development defines T cell repertoire formation 96%
Similar papers in this journal
- Single-Cell Multiomics Defines Tolerogenic Extrathymic Aire-Expressing Populations with Unique Homology to Thymic Epithelium 96%
- A reservoir of stem-like CD8 T cells in the tumor-draining lymph node maintains the ongoing anti-tumor immune response 95%
- Integrated single-cell transcriptomics and epigenomics reveals strong germinal center-associated etiology of autoimmune risk loci 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.