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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89297 |
| Date | 26 January 2024 |
| Creators | Wolf, Johannes, Willscher, Edith, Loeffler-Wirth, Henry, Schmidt, Maria, Flemming, Gunter, Zurek, Marlen, Uhlig, Holm H., Händel, Norman, Binder, Hans |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2551 |
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