Evidence map›Paper›PMID 42032651›Full record

Trial reportBMC medicine2026

Therapeutic TG2 inhibition reverses systemic multiomic dysregulation in celiac disease.

Valeriia Dotsenko, Hana Hien Le, Sonja Rajić, Robert Moulder, Jalmari Kettunen, M Karoliina Hirvonen, Alex M Dickens, Tuulia Hyötyläinen, Bernhard Tewes, Timo Zimmermann and 11 more

Abstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in BMC medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Valeriia DotsenkoCeliac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland.
Hana Hien LeCeliac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland.
Sonja RajićMolecular Epidemiology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Robert MoulderTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Jalmari KettunenTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
M Karoliina HirvonenTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Alex M DickensTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Tuulia HyötyläinenSchool of Science and Technology, Örebro University, Örebro, Sweden.
Bernhard TewesDr. Falk Pharma GmbH, Freiburg, Germany.
Timo ZimmermannDr. Falk Pharma GmbH, Freiburg, Germany.
Ralf MohrbacherDr. Falk Pharma GmbH, Freiburg, Germany.
Tomi SuomiTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center, Tampere, Finland.
Riitta LahesmaaTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Matej OrešičTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Laura L EloTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Emma RaitoharjuMolecular Epidemiology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Detlef SchuppanInstitute of Translational Immunology and Celiac Center, Medical Center, Johannes-Gutenberg University, Mainz, Germany.
Markku MäkiCeliac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland.
Keijo ViiriCeliac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland. keijo.viiri@tuni.fi.
CEC-3 Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCeliac disease (CeD) is an autoimmune disease triggered by dietary gluten in genetically predisposed individuals. Deamidation of gluten peptides by the CeD autoantigen and enzyme transglutaminase 2 (TG2) is central to the pathogenesis of CeD. Inhibition of TG2 with the specific inhibitor ZED1227 effectively prevents gluten-induced histological damage in CeD patients. Here we aimed to explore the systemic plasma lipidomic, proteomic and DNA methylomic changes in ZED1227-treated CeD patients undergoing a gluten challenge.

methodsIndividuals with CeD on a long-term gluten-free diet (GFD) underwent a 6-week gluten challenge combined with daily 100 mg ZED1227 drug (PGCd, n = 28) or placebo (PGCp, n = 19). Samples were collected at baseline (GFD) and post-gluten challenge (PGC). Mass spectrometry-based lipidomic and proteomics profiling were applied to plasma samples matched with duodenal histology. Whole blood samples (drug, n = 20; placebo, n = 16) were subjected to DNA methylation analysis. Comparative analyses were performed between the groups, with adjustment for BMI, age, sex, and country of origin.

resultsSignificantly different gluten-induced plasma lipidomic changes were detected between GFD vs. PGCp and between GFD vs. PGCd, with 46 lipids differentially expressed in the placebo group and 6 in the drug group suggesting that the ZED1227 normalized gluten-induced lipidomic changes in plasma. Changes in medium-chain fatty acylcarnitines (CARs), particularly CAR 10:1 and CAR 9:0, were correlated with transient, non–clinically significant changes in renal biomarkers, with kidney function remaining within the normal range in the PGCp group. Glomerular filtration rate and plasma creatinine were restored with ZED1227. Integrated multi-omics analysis revealed a coordinated immune–epigenetic–lipid module centered on Ficolin-2, PUFA-enriched triglycerides, and a tightly co-regulated CpG cluster in the PER3 circadian regulator gene, highlighting selective immunometabolic coupling independent of clinical stratification. Drug treatment revealed consistent patterns suggesting normalization of the proteome and DNA methylome indicating that ZED1227 attenuated the systemic responses to gluten challenge.

conclusionsThese findings provide evidence that ZED1227 can significantly prevent the gluten-induced CeD-associated systemic changes in plasma/blood. CLINICAL TRIAL: EudraCT 2017-002241-30.

Indexed as

Celiac DiseaseGTP-Binding ProteinsTransglutaminasesDiet, Gluten-FreeDNA MethylationFemaleGlutensHumansLipidomicsMaleMultiomicsProtein Glutamine gamma Glutamyltransferase 2ProteomicsGlutensGTP-Binding ProteinsProtein Glutamine gamma Glutamyltransferase 2TransglutaminasesBiomarkersCeliac diseaseDNA methylationEpigeneticsPlasma lipidomicsProteomicsTransglutaminase 2

Identifiers

PMID42032651

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.