Circulating microRNAs as novel non-invasive biomarkers of paediatric celiac disease and adherence to gluten-free diet.

Carlo Catassi, Marco Silano, Cristina Felli, Antonella Baldassarre, Paolo Uva, Anna Alisi, Davide Cangelosi, Monica Ancinelli, Mariangela Caruso, Alessandro Paolini, Alessia Montano, Olimpia Vincentini, Elena Lionetti, Simona Gatti, Francesca Ferretti, Andrea Masotti

Journal: EBioMedicine 2022;76():103851

PMID: 35151110

Free Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Celiac Disease (CD) is a multifactorial autoimmune enteropathy (with a prevalence of approximately 1% worldwide) that exhibits a wide spectrum of clinical, serological and histological manifestations. For the diagnosis of paediatric CD, the gold standard is the combination of serological tests (with high TGA-IgA values greater than 10 times the upper limit of normal) and duodenal biopsy (with a positive TGA-IgA but low titer). Therefore, a diagnostic test that totally excludes an invasive approach has not been discovered so far and the discovery of novel biological markers would represent an undoubted advantage for the diagnosis of CD and prognostic evaluation. MicroRNAs (miRNAs), small non-coding RNAs (18-22 nucleotides) that regulate gene expression at post-transcriptional level and play important roles in many biological processes, represent a novel class of potential disease biomarkers. Their presence in biological fluids (i.e., serum, plasma, saliva, urine) provides the opportunity to employ circulating miRNAs as novel non-invasive biomarkers.

METHODS

In our prospective observational study, we examined the expression of circulating miRNAs in a cohort of CD patients (both at diagnosis and on gluten-free diet, respectively referred as CD and GFD) compared to healthy controls. By small RNA-Seq we discovered a set of circulating miRNAs that were further validated by qPCR with specific assays.

FINDINGS

We found that out of the 13 miRNAs able to discriminate the three groups (i.e., CD, GFD and controls), three of them, namely miR-192-5p, miR-215-5p and miR-125b-5p (alone or in combination), were able to discriminate these three groups with high accuracy and specificity.

INTERPRETATION

Our conclusions emphasize that these circulating miRNAs can be employed not only for the diagnosis of CD patients with a low TGA-IgA titer but also to monitor the adherence to a gluten-free diet by CD patients. In conclusion, we suggest the use of the circulating miRNAs identified in this work as a novel diagnostic and follow-up tool for paediatric CD.

FUNDING

This work was supported by Fondazione Celiachia Onlus (FC) Grant n° 018/FC/2013 and by Italian Ministry of Health (Ricerca Corrente).

Address: Research Laboratories, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy.; Clinical Bioinformatics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.; Research Laboratories, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy; Research Unit of Molecular Genetics of Complex Phenotypes, Research Laboratories, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy.; Hepato-Gastroenterology and Nutrition Department, Research Laboratories, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy.; Department of Maternal Infantile and Urological Sciences, SAPIENZA University of Rome, Rome, Italy.; Unit of Human Nutrition and Health, Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy.; Department of Pediatrics, Polytechnic University of Marche, Ancona, Italy.; Research Laboratories, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy. Electronic address: [email protected].

DOI: 10.1016/j.ebiom.2022.103851