Salivary Proteomics Reveals Disease- and Therapy-Associated Molecular Patterns in Relapsing-Remitting Multiple Sclerosis
4 affiliations
- 1Department of Life and Environmental Sciences, University of Cagliari, 09121 Cagliari, Italy
- 2Multiple Sclerosis Center, Binaghi Hospital, ASL Cagliari, University of Cagliari, 09126 Cagliari, Italy
- 3Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- 4Department of Biomedical Sciences, University of Cagliari, 09121 Cagliari, Italy
Abstract
Multiple sclerosis (MS) is a chronic immune-mediated disease for which non-invasive biomarkers, able to detect disease- and treatment-associated molecular changes, are needed. We characterized the whole-saliva proteome of patients with relapsing-remitting (RR) MS at baseline before treatment initiation (MS-T0; n = 66) and after six months of disease-modifying therapy (MS-T1; n = 40), in comparison with healthy controls (HC; n = 31). Nano-liquid chromatography-high-resolution tandem mass spectrometry identified 1305 proteins, of which 209 differed among the main comparisons. Pairwise and paired analyses distinguished persistent RRMS-associated alterations, baseline-attenuation patterns with changes shifting towards HC levels, treatment-associated differences emerging at MS-T1, and longitudinal-only alterations. The identified patterns are descriptive and cannot be interpreted as evidence of pharmacological treatment effects or clinical response. The existence of specific RRMS alterations was supported by exploratory Random Forest, which classified HC, MS-T0 and MS-T1 samples using a panel of 50 proteins, most of which (96%) also showed significant changes in univariate tests. Reactome enrichment evidenced that proteins pertaining to the identified patterns are mainly involved in innate immunity, neutrophil degranulation, cell-death pathways, cytokine signalling, and protein folding. These findings indicate that six months of therapy was associated with substantial salivary proteome changes and support saliva as a candidate biofluid for longitudinal molecular monitoring and non-invasive detection of treatment-associated salivary proteome variations in RRMS.
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BibTeX
@article{guadalupi2026salivary,
title = {{Salivary Proteomics Reveals Disease- and Therapy-Associated Molecular Patterns in Relapsing-Remitting Multiple Sclerosis}},
author = {Giulia Guadalupi and Cristina Contini and Chiara Piras and Giada Pisano and Jessica Frau and Giuseppe Fenu and Giancarlo Coghe and Greca Lai and Massimo Castagnola and Irene Messana and Giacomo Diaz and Tiziana Cabras and Alessandra Olianas and Eleonora Cocco and Barbara Manconi and Lorena Lorefice},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101524},
url = {https://www.mdpi.com/2218-273X/16/10/1524},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Salivary Proteomics Reveals Disease- and Therapy-Associated Molecular Patterns in Relapsing-Remitting Multiple Sclerosis
AU - Giulia Guadalupi
AU - Cristina Contini
AU - Chiara Piras
AU - Giada Pisano
AU - Jessica Frau
AU - Giuseppe Fenu
AU - Giancarlo Coghe
AU - Greca Lai
AU - Massimo Castagnola
AU - Irene Messana
AU - Giacomo Diaz
AU - Tiziana Cabras
AU - Alessandra Olianas
AU - Eleonora Cocco
AU - Barbara Manconi
AU - Lorena Lorefice
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101524
UR - https://www.mdpi.com/2218-273X/16/10/1524
AB - Multiple sclerosis (MS) is a chronic immune-mediated disease for which non-invasive biomarkers, able to detect disease- and treatment-associated molecular changes, are needed. We characterized the whole-saliva proteome of patients with relapsing-remitting (RR) MS at baseline before treatment initiation (MS-T0; n = 66) and after six months of disease-modifying therapy (MS-T1; n = 40), in comparison with healthy controls (HC; n = 31). Nano-liquid chromatography-high-resolution tandem mass spectrometry identified 1305 proteins, of which 209 differed among the main comparisons. Pairwise and paired analyses distinguished persistent RRMS-associated alterations, baseline-attenuation patterns with changes shifting towards HC levels, treatment-associated differences emerging at MS-T1, and longitudinal-only alterations. The identified patterns are descriptive and cannot be interpreted as evidence of pharmacological treatment effects or clinical response. The existence of specific RRMS alterations was supported by exploratory Random Forest, which classified HC, MS-T0 and MS-T1 samples using a panel of 50 proteins, most of which (96%) also showed significant changes in univariate tests. Reactome enrichment evidenced that proteins pertaining to the identified patterns are mainly involved in innate immunity, neutrophil degranulation, cell-death pathways, cytokine signalling, and protein folding. These findings indicate that six months of therapy was associated with substantial salivary proteome changes and support saliva as a candidate biofluid for longitudinal molecular monitoring and non-invasive detection of treatment-associated salivary proteome variations in RRMS.
SN - 2218-273X
ER -