Next Article in Journal
Comprehensive Analysis of Correlations in the Expression of miRNA Genes and Immune Checkpoint Genes in Bladder Cancer Cells
Previous Article in Journal
Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model
Previous Article in Special Issue
Gliadin, through the Activation of Innate Immunity, Triggers lncRNA NEAT1 Expression in Celiac Disease Duodenal Mucosa
Open AccessArticle

Deciphering the Transcriptomic Heterogeneity of Duodenal Coeliac Disease Biopsies

1
Department of Laboratory Medicine at Hospital “St. Georg” Leipzig, 04129 Leipzig, Germany
2
Immuno Deficiency Centre Leipzig (IDCL) at Hospital St. Georg Leipzig, Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiency Diseases, 04129 Leipzig, Germany
3
IZBI, Interdisciplinary Centre for Bioinformatics, University Leipzig, Härtelstr. 16–18, 04107 Leipzig, Germany
4
Paediatric Gastroenterology Unit, University Hospital for Children and Adolescents, 04103 Leipzig, Germany
5
Children’s Hospital of the Clinical Centre “Sankt Georg”, 04129 Leipzig, Germany
6
Translational Gastroenterology Unit, Oxford NIHR Biomedical Research Centre, Experimental Medicine, Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Oxford OX4 2PG, UK
*
Author to whom correspondence should be addressed.
Contributed equally.
Academic Editor: Konrad Huppi
Int. J. Mol. Sci. 2021, 22(5), 2551; https://doi.org/10.3390/ijms22052551
Received: 21 January 2021 / Revised: 2 March 2021 / Accepted: 3 March 2021 / Published: 4 March 2021
(This article belongs to the Special Issue Molecular Research on Celiac Disease)
Coeliac disease (CD) is a clinically heterogeneous autoimmune disease with variable presentation and progression triggered by gluten intake. Molecular or genetic factors contribute to disease heterogeneity, but the reasons for different outcomes are poorly understood. Transcriptome studies of tissue biopsies from CD patients are scarce. Here, we present a high-resolution analysis of the transcriptomes extracted from duodenal biopsies of 24 children and adolescents with active CD and 21 individuals without CD but with intestinal afflictions as controls. The transcriptomes of CD patients divide into three groups—a mixed group presenting the control cases, and CD-low and CD-high groups referring to lower and higher levels of CD severity. Persistence of symptoms was weakly associated with subgroup, but the highest marsh stages were present in subgroup CD-high, together with the highest cell cycle rates as an indicator of virtually complete villous atrophy. Considerable variation in inflammation-level between subgroups was further deciphered into immune cell types using cell type de-convolution. Self-organizing maps portrayal was applied to provide high-resolution landscapes of the CD-transcriptome. We find asymmetric patterns of miRNA and long non-coding RNA and discuss the effect of epigenetic regulation. Expression of genes involved in interferon gamma signaling represent suitable markers to distinguish CD from non-CD cases. Multiple pathways overlay in CD biopsies in different ways, giving rise to heterogeneous transcriptional patterns, which potentially provide information about etiology and the course of the disease. View Full-Text
Keywords: molecular subgroups; gene expression signatures; villous atrophy; immune cell de-convolution; machine learning; self-organizing maps; personalized diagnostics molecular subgroups; gene expression signatures; villous atrophy; immune cell de-convolution; machine learning; self-organizing maps; personalized diagnostics
Show Figures

Graphical abstract

MDPI and ACS Style

Wolf, J.; Willscher, E.; Loeffler-Wirth, H.; Schmidt, M.; Flemming, G.; Zurek, M.; Uhlig, H.H.; Händel, N.; Binder, H. Deciphering the Transcriptomic Heterogeneity of Duodenal Coeliac Disease Biopsies. Int. J. Mol. Sci. 2021, 22, 2551. https://doi.org/10.3390/ijms22052551

AMA Style

Wolf J, Willscher E, Loeffler-Wirth H, Schmidt M, Flemming G, Zurek M, Uhlig HH, Händel N, Binder H. Deciphering the Transcriptomic Heterogeneity of Duodenal Coeliac Disease Biopsies. International Journal of Molecular Sciences. 2021; 22(5):2551. https://doi.org/10.3390/ijms22052551

Chicago/Turabian Style

Wolf, Johannes; Willscher, Edith; Loeffler-Wirth, Henry; Schmidt, Maria; Flemming, Gunter; Zurek, Marlen; Uhlig, Holm H.; Händel, Norman; Binder, Hans. 2021. "Deciphering the Transcriptomic Heterogeneity of Duodenal Coeliac Disease Biopsies" Int. J. Mol. Sci. 22, no. 5: 2551. https://doi.org/10.3390/ijms22052551

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop