Circulating miRNAs as potential early predictors of T1D onset in celiac disease patients

Grant: 008/2024

• Title: Circulating miRNAs as potential early predictors of T1D onset in celiac disease patients.
• Duration: 3 Years Project
• Principal Investigator: Andrea Masotti, Bambino Gesù Children’s Hospital-IRCCS, Rome, Italy

THE STUDY

Background

This project aims to discover circulating microRNAs (miRNAs) in diabetic patients with celiac disease, to identify early predictors of diabetes in celiac patients. Celiac disease and diabetes share common autoimmune mechanisms and genetic predispositions, which suggests a potential overlap in their pathogenesis. Circulating miRNAs are small, stable, and easily detectable in blood, making them ideal candidates for non-invasive biomarkers. By profiling miRNAs in this specific cohort, we will identify unique miRNA signatures that correlate with the early stages of diabetes, allowing a timely intervention, reducing the risk of fatal events of ketoacidosis and/or permanent ilnesses, thus improving patient outcomes.

Hypothesis, Rationale and Aims

Hypothesis: circulating miRNAs and their expression profiles by exhibiting distinct patterns in T1D patients with CD, can be exploited as early predictors for the onset of diabetes in CD patients.

Rationale: CD and T1D are autoimmune disorders that share common genetic risk factors, immune-mediated mechanisms, co-occurrence and environmental triggers.

Circulating miRNAs are small, non-coding RNAs emerged as stable, non-invasive biomarkers for various diseases and autoimmune disorders. Specific miRNA signatures may reflect early changes in molecular processes that precede the onset of T1D in CD patients. Identifying these miRNA signatures could allow for the development of a predictive tool for diabetes risk, enabling timely intervention in this high-risk population.

Aims: 1) To profile circulating miRNA expression in T1D patients with and without CD, to identify miRNAs associated with T1D onset. 2) To study the relationship between miRNA expression changes and the development of T1D in CD patients, identifying miRNAs that precede clinical diagnosis. 3) To propose a set of potential miRNA biomarkers for a further validation in an independent cohort of CD patients.

Research Plan (Experimental design and Methodologies)

The experimental design of the project has two main tasks:

Task 1: Recruitment of a well-defined cohort of T1D patients, with and without CD. Collection of blood samples for miRNA analysis. Patients will be divided into five groups: 1) CD patients with T1D (n=30), 2) Diabetic patients (n=30), 3) active CD patients (n=30), 4) CD patients under gluten-free diet (n=30), and 5) healthy controls (n=30).

Task 2: miRNA Profiling and Data Analysis. We will compare miRNA profiles between the different groups in order to find dysregulated miRNAs in T1D patients with or without CD compared to CD patients alone and/or healthy individuals. We will identify those miRNAs potentially “activated” in T1D patients that could early predict the onset of this disease in CD patients at a certain time after the diagnosis.

Methodologies to be used:

We will use the same workflow that we used in our past project (funded by AIC) and reported in our recent publication. Briefly, we will perform a qPCR profiling of circulating miRNAs and we will statistically analyse the data to extract the most relevant predictors of T1D in the CD group, in order to study their relevance as early biomarkers.

Expected results and Impact on Celiac disease

The project aims to identify specific miRNA signatures differentially expressed in celiac patients with or without diabetes, offering insights into immune regulation, inflammation, and glucose metabolism. These miRNAs will be investigated as potential biomarkers for diabetes prediction. Longitudinal follow-up will assess their utility in predicting diabetes onset, potentially leading to a non-invasive blood test.

This innovative approach could pioneer miRNA-based early diabetes prediction in celiac patients, advancing personalized medicine and patient outcomes. The project may provide new insights into the molecular mechanisms linking CD and T1D, aiding the development of targeted therapies.