New Markers of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Function in Sweat

MucoSWEATomics New Markers of CFTR Function in Sweat: Value for Diagnosis and Efficacy of Target Therapies

Sweat is a watery solution containing trace amounts of proteins and peptides that may contribute to the antimicrobial defense system of the skin barrier, playing a role in innate immune responses against potential pathogens. The peptide and metabolite composition of sweat has not been fully explored. Evidence suggests that the composition of the skin barrier could vary with diseases. The causes and consequences of the changes of sweat proteins and peptides in humans are unknown. This clinical trial will focus on multiomics analysis of sweat, mainly of the antimicrobial peptides that play a key role in the host-pathogen interaction. Antioxidants, anti-bacterial and anti-inflammatory compounds may contribute to the regulation of systemic inflammation and pathophysiological disorders. In cystic fibrosis, inflammatory responses are altered, exaggerated and persistent, even in the absence of infection. It is therefore relevant to study the influence of CFTR mutations on the profile of antimicrobial peptides expressed in sweat. The clinical study will potentially lead to the discovery of novel non-invasive biomarkers of the disease in sweat.

The assessment of the quantity of sweat secreted will be measured in mg with a scale, the sweat chloride concentration will be done by coulometric titration and expressed in mmol/L.

The quantity of total protein will be analysed with a colorimetric assay and will be expressed in mg/ml. The identification of the different protein will be performed with different software, databases and algorithms such as Proteome Discoverer (version 1.4.1.14), Mascot software (version 2.2.0.6), MaxQuant (version 1.5.2.8), Andromeda, Uniprot, LFQ and Perseus (version 1.5.0.15).

Inclusion Criteria: Subject aged of 18 years or more. The patients with cystic fibrosis must have a confirmed diagnosis, be clinically stable, have a Forced Expiratory Volume in one second (FEV1) ≥ 30 and an O2 saturation ≥ 92%. F508del homozygous will been tested. Heterozygosity (parents of patients) will be confirmed by the presence of a single F508del mutation. Exclusion Criteria: Presence of an acute infection Pregnancy and lactation Subjects currently included in another clinical trial Subjects with forearm skin alterations Subjects with signs of dehydration Smokers