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The expression levels of CHI3L1 and IL15Rα correlate with TGM2 in duodenum biopsies of patients with celiac disease

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Abstract

Objective and design

Celiac disease (CD) is an intestinal inflammatory disorder of the small intestine. Gliadins are a component of gluten and there are three main types (α, γ, and ω). Recent studies indicate that gliadin peptides are able to activate an innate immune response. IL15 is a major mediator of the innate immune response and is involved in the early alteration of CD mucosa. The chitinase molecules are highly expressed by the innate immune cells during the inflammatory processes.

Material or subjects

We analyzed several microarray datasets of PBMCs and duodenum biopsies of CD patients and healthy control subjects (HCs). We verified the modulation CHI3L1 in CD patients and correlated the expression levels to the IL15, IL15Rα, TGM2, IFNγ, and IFNGR1/2. Duodenal biopsy samples belonged to nine active and nine treated children patients (long-term effects of gliadin), and 17 adult CD patients and 10 adults HCs. We also selected 169 samples of PBMCs from 127 CD patients on adherence to a gluten-free diet (GFD) for at least 2 years and 44 HCs.

Results

Our analysis showed that CHI3L1 and IL15Rα were significantly upregulated in adult and children’s celiac duodenum biopsies. In addition, the two genes were correlated significantly both in children than in adults CD duodenum biopsies. No significant modulation was observed in PBMCs of adult CD patients compared to the HCs. The correlation analysis of the expression levels of CHI3L1 and IL15Rα compared to TGM showed significant values both in adults and in children duodenal biopsies. Furthermore, the IFNγ expression levels were positively correlated with CHI3L1 and IL15Rα. Receiver operating characteristic (ROC) analysis confirmed the diagnostic ability of CHI3L1 and IL15Rα to discriminate CD from HCs.

Conclusion

Our data suggest a role for CHI3L1 underlying the pathophysiology of CD and represent a starting point aiming to inspire new investigation that proves the possible use of CHI3L1 as a diagnostic factor and therapeutic target.

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Abbreviations

CD:

Celiac disease

LP:

Lamina propria

CHIT1:

Chitotriosidase

CHIA:

Acidic mammalian chitinase

CHI3L1:

Chitinase 3-like-1

CHI3L2:

Chitinase 3-like-2

CHID1:

Chitinase domain-containing 1

IL15:

Interleukin 15

(tTG)(TGM2):

Tissue transglutaminase

APC:

Antigen presenting cells

IFNγ:

Interferon gamma

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Acknowledgements

We would like to show our gratitude to the authors of microarray datasets made available online, for consultation and re-analysis. In addition, I would like to express my gratitude to Oliver Di Rosa, an inspiration in my life.

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Authors and Affiliations

  1. Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Via S. Sofia 87, 95125, Catania, Italy

    Paola Catrogiovanni, Giuseppe Musumeci, Salvatore Giunta, Rosa Imbesi & Michelino Di Rosa

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  1. Paola Catrogiovanni
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  2. Giuseppe Musumeci
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Correspondence to Michelino Di Rosa.

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Catrogiovanni, P., Musumeci, G., Giunta, S. et al. The expression levels of CHI3L1 and IL15Rα correlate with TGM2 in duodenum biopsies of patients with celiac disease. Inflamm. Res. 69, 925–935 (2020). https://doi.org/10.1007/s00011-020-01371-9

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