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Overexpression of endogenous retroviruses in children with celiac disease

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Abstract

Human endogenous retroviruses (HERVs) represent 8% of our genome. Although no longer infectious, they can regulate transcription of adjacent cellular genes, produce retroviral RNAs, and encode viral proteins that can modulate both innate and adaptive immune responses. Based on this, HERVs have been studied and proposed as contributing factors in various autoimmune disorders. Celiac disease (CD) is considered an autoimmune disease, but HERV expression has not been studied in celiac patients. The aim of this study is to assess the transcription levels of pol genes of HERV-H, -K, and -W and of their TRIM28 repressor in WBCs from celiac children and age-matched control subjects. A PCR real-time TaqMan amplification assay was used to evaluate HERV and TRIM28 transcripts with normalization of the results to glyceraldehyde-3-phosphate dehydrogenase. The RNA levels of pol genes of the three HERV families were significantly higher in WBCs from 38 celiac patients than from 51 control subjects. TRIM28 transcription was comparable between the two study populations.

Conclusion: Present results show, for the first time, that pol genes of HERV-H, -K, and -W are overexpressed in patients with CD. Given their proinflammatory and autoimmune properties, this suggests that HERVs may contribute to the development of CD in susceptible individuals.

What is Known:

• Based on this, HERVs have been studied and proposed as contributing factors in various autoimmune disorders.

What is New:

• Present results show, for the first time, that pol genes of HERV-H, -K, and -W are overexpressed in patients with CD.

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Data availability

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Code availability

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Abbreviations

CD:

Celiac disease

HERVs :

Human endogenous retroviruses

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

KRAB-ZNFs:

Krüppel-associated box domain-zinc finger proteins

MS:

Multiple sclerosis

PRRs:

Pattern recognition receptors

SUMO:

Small ubiquitin-like modifier

SNPs:

Single-nucleotide polymorphisms

T1D:

Type 1 diabetes

WBCs:

White blood cells

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Acknowledgements

We thank Dr. Hervé Perron (Geneuro-Innovation & University of Lyon, France) for his critical revision of the manuscript and helpful comments.

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Authors and Affiliations

  1. Department of Public Health and Pediatric Sciences, University of Turin, Piazza Polonia, 96 10126, Turin, Italy

    Pier-Angelo Tovo & Massimiliano Bergallo

  2. Pediatric Gastroenterology Unit, Regina Margherita Children’s Hospital, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy

    Anna Opramolla, Antonio Pizzol, Giulia Calosso, Michele Pinon, Fabio Cisarò, Caterina Rigazio & Pier Luigi Calvo

  3. Pediatric Laboratory, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy

    Valentina Daprà, Ilaria Galliano, Cristina Calvi & Massimiliano Bergallo

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  1. Pier-Angelo Tovo
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Contributions

PA and MB developed the theory, contributed to the design and implementation of the research, and write the manuscript. IG and VD contributed with the statistical analysis. AO, MP, CR, AP, and GC contributed to the design and implementation of the research and revised the manuscript. FC revised the manuscript. CC performed the experiment. All authors approved the final manuscript as submitted.

Corresponding author

Correspondence to Massimiliano Bergallo.

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All procedures performed were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Communicated by Peter de Winter

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Tovo, PA., Opramolla, A., Pizzol, A. et al. Overexpression of endogenous retroviruses in children with celiac disease. Eur J Pediatr 180, 2429–2434 (2021). https://doi.org/10.1007/s00431-021-04050-x

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