Phenotyping multiple subsets in Sjögren's syndrome: a salivary proteomic SWATH-MS approach towards precision medicine

干燥综合征多个亚型的表型分析:唾液蛋白质组学 SWATH-MS 方法实现精准医疗

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作者:Antonella Cecchettini #, Francesco Finamore #, Nadia Ucciferri, Valentina Donati, Letizia Mattii, Enza Polizzi, Francesco Ferro, Francesca Sernissi, Marta Mosca, Stefano Bombardieri, Silvia Rocchiccioli, Chiara Baldini

Background

This proof of concept study was aimed at characterizing novel salivary biomarkers specific for different subsets in primary Sjögren's syndrome (pSS) in order to improve patients' profiling.

Conclusions

Constellations of proteins, including S100A proteins, characterize different pSS subsets reflecting either salivary gland dysfunction or inflammation. Salivary proteomics may foster future research projects ultimately aimed at developing personalized treatments for pSS patients.

Methods

pSS patients were stratified in three subgroups according to both (a) focus score in the minor salivary gland biopsies (i.e. intensity of immune cell infiltration in the tissue) and (b) unstimulated salivary flow rate. Healthy volunteers were included as controls. A nano-HPLC-SWATH-MS approach was used for the analysis of saliva proteome of different subsets.

Results

We found 203 differentially expressed proteins in pSS patients with respect to controls with evident differences in the expression of normal constituents of the human salivary proteome (i.e. prolactin-inducible protein, proline-rich proteins, cystatins) and several mediators of inflammatory processes. The comparative analysis of the pSS phenotypes unrevealed 63 proteins that were shared and specifically modulated in the three subsets of pSS patients converging on several inflammatory pathways. Among them S100A protein appeared of particular interest merging on IL-12 signaling and being significantly influenced by either salivary flow impairment or intensity of immune cell infiltration in the tissue. Conclusions: Constellations of proteins, including S100A proteins, characterize different pSS subsets reflecting either salivary gland dysfunction or inflammation. Salivary proteomics may foster future research projects ultimately aimed at developing personalized treatments for pSS patients.

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