Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells From Pediatric Coeliac Disease Patients Suggests Potential Pre-Seroconversion Markers
| Autor: | Aarón D. Ramírez-Sánchez, Xiaojing Chu, Rutger Modderman, Yvonne Kooy-Winkelaar, Sibylle Koletzko, Ilma R. Korponay-Szabó, Riccardo Troncone, Cisca Wijmenga, Luisa Mearin, Sebo Withoff, Iris H. Jonkers, Yang Li |
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| Přispěvatelé: | Ramirez-Sanchez, A. D., Chu, X., Modderman, R., Kooy-Winkelaar, Y., Koletzko, S., Korponay-Szabo, I. R., Troncone, R., Wijmenga, C., Mearin, L., Withoff, S., Jonkers, I. H., Li, Y., Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Molecular Neuroscience and Ageing Research (MOLAR) |
| Rok vydání: | 2021 |
| Předmět: |
Leukocytes
Mononuclear/metabolism pre-diagnostic biomarkers Sequence Analysis RNA Immunology fungi PBMC Biomarker scRNAseq Celiac Disease Seroconversion Celiac Disease/diagnosis Leukocytes Mononuclear/metabolism Leukocytes Mononuclear Immunology and Allergy RNA Humans Atrophy differential gene expression Child Sequence Analysis pre-diagnostic biomarker Biomarkers Human |
| Zdroj: | Frontiers in Immunology, 13:843086. Frontiers Media SA Frontiers in Immunology, 13. FRONTIERS MEDIA SA |
| ISSN: | 1664-3224 |
| Popis: | Celiac Disease (CeD) is a complex immune disorder involving villous atrophy in the small intestine that is triggered by gluten intake. Current CeD diagnosis is based on late-stage pathophysiological parameters such as detection of specific antibodies in blood and histochemical detection of villus atrophy and lymphocyte infiltration in intestinal biopsies. To date, no early onset biomarkers are available that would help prevent widespread villous atrophy and severe symptoms and co-morbidities. To search for novel CeD biomarkers, we used single-cell RNA sequencing (scRNAseq) to investigate PBMC samples from 11 children before and after seroconversion for CeD and 10 control individuals matched for age, sex and HLA-genotype. We generated scRNAseq profiles of 9559 cells and identified the expected major cellular lineages. Cell proportions remained stable across the different timepoints and health conditions, but we observed differences in gene expression profiles in specific cell types when comparing patient samples before and after disease development and comparing patients with controls. Based on the time when transcripts were differentially expressed, we could classify the deregulated genes as biomarkers for active CeD or as potential pre-diagnostic markers. Pathway analysis showed that active CeD biomarkers display a transcriptional profile associated with antigen activation in CD4+ T cells, whereas NK cells express a subset of biomarker genes even before CeD diagnosis. Intersection of biomarker genes with CeD-associated genetic risk loci pinpointed genetic factors that might play a role in CeD onset. Investigation of potential cellular interaction pathways of PBMC cell subpopulations highlighted the importance of TNF pathways in CeD. Altogether, our results pinpoint genes and pathways that are altered prior to and during CeD onset, thereby identifying novel potential biomarkers for CeD diagnosis in blood. |
| Databáze: | OpenAIRE |
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