the EXPOSITION Study

University of Pavia200 enrolled

Overview

This is a cross-sectional study to evaluate the variation of biological biomarkers of oxidative stress and inflammation in response to the external exposome, in people with Multiple Sclerosis (pwMS).The objective is to study the variation of biological biomarkers of oxidative stress and inflammation in response to external exposome in pwMS, controlling for other biomarkers (cytokine, neurofilaments, microbiome), gender, age, anthropometric measurements, vitamin D levels and medical history. Specifically, the variation of microRNAs is defined as the primary outcome, in response to urban air pollution, urbanization, lifestyle and quality of life components of the external exposome. Following the functional exposome approach:(1)Information on a pwMS sample about socio-demographic characteristics and medical history will be collected and specific components of the (2) On the same pwMS sample, the internal exposome variation will be measured. MicroRNA levels and gut and nasal microbiota alpha- and beta-diversity and relative bacterial abundances will be considered as biomarkers of oxidative stress and inflammation. At the same time, cytokines and neurofilament proteins (NfL) will be measured as biomarkers of neurodegeneration and axonal damage. Adults (≥ 18 years) pwMS, with relapsing-remitting course, diagnosis of MS according to 2017 McDonald criteria and residing in Pavia or Milan (Italy) will be included. Potentially eligible pwMS will be screened by a neurologist expert in MS who will verify that all the inclusion criteria will be fulfilled. To validate variation among 7 selected MS diagnostic miRNA, in response to urban air pollution, urbanization, lifestyle and quality of life components of the external exposome, the differential expression (ΔCT) for each miRNA will be considered as the outcome measure. Two hundred eligible pwMS who meet the inclusion criteria and sign the informed consent will be included in the study, to consider 15% dropout at the blood sampling stage.

Study Type

OBSERVATIONAL

Enrollment

200

Conditions

Multiple Sclerosis, Relapsing-Remitting

Outcomes

Primary Outcomes

microRNAs

The differential expression of a set of 7 specific circulating plasma microRNAs from the blood of each pwMS will be measured. The set of miRNAs has been already selected based on their significant deregulated expression in MS, as evidenced in a bioinformatic analysis conducted using computational resources. A portion of serum samples will be collected and immediately frozen at -20°C. After being transported, serum samples will be thawed and the circulating RNAs will be extracted. After a step of microRNA specific reverse transcription, the copy-DNA obtained will be used as the template for Real Time-qPCR analyses of selected miRNAs by Singleplex TaqMan microRNA assay reactions.The method of Livak et al. will be applied for the comparative analysis of the relative expression of the selected microRNAs in serum samples, considering different combinations of the external exposome variables.

Time frame: from March 2024 to July 2024 visit

Air quality

Spatial information on pollutants such as PM10, PM2.5, PM1.0 expressed in microg/m3, nanoparticulate (n/cm3), and black carbon (microg/m3) from CAMS and CHIMBO databases and from Sentinel-5P TROPOMI will be included as gridded emissions in 0.1° x 0.1° (long-lat) resolution for the whole time series (daily values), from March 2023 onwards from the Pavia and Milano provinces. Large Eddy Simulations will be carried out over such areas with a high spatial-temporal resolution for estimating - in a quantitative manner - the 3D pollutants concentration at the street level.The grid will be further subdivided into the municipalities of the two provinces and a "personal exposure" will be also assessed, based on the geographic position of each pwMS derived from the residence address (geo-positioning).

Time frame: from March 2023 to July 2023

Nutritional assessment

The dietary habits of the participants will be evaluated with the use of a validated food frequency questionnaire (FFQ) adapted to the Italian population and adjusted based on current food trends, such as the consumption of plant-based milk and meat. Detailed information about the daily food consumption of pwMS will be gained through a 24-h dietary recall.