Extracellular Vesicles in Primary Sjögren’s Syndrome: A Promising Source for Novel Proteomic Biomarkers

Chiara Baldini¹, Francesco Finamore ², Francesco Ferro ¹, Silvia Rocchiccioli ², Marta Mosca ³, Letizia Mattii ⁴ and Antonella Cecchettini ⁴, ¹Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, Pisa, Italy, ²National Research Council – Clinical Institute of Physiology, PISA, Italy, ³Rheumatology Unit, Department of clinical and experimental medicine, University of Pisa, Pisa, Italy, ⁴University of Pisa, Pisa, Italy

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: salivary hypofunction and proteomics, Sjogren's syndrome

Session Information

Date: Tuesday, November 12, 2019

Session Title: Sjögrenʼs Syndrome – Basic & Clinical Science Poster I

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Primary Sjögren’s syndrome (pSS) is a complex autoimmune disorder characterized by the specific involvement of salivary and lachrymal glands. In the recent past several attempts have been made by using a proteomic approach to identify valid biomarkers for pSS in whole saliva. Extracellular vesicle (EVs) include exosomes, microvesicles and apoptotic body. Little is known about the potential advantages of EVs proteomics compared to the overall traditional concept of analyzing the proteome of whole saliva nor to what extent their content may reflect the phenotypic state of pSS. In this study, we used a sequential window acquisition of all the theoretical fragment ion spectra (SWATH-MS) approach to monitor the dynamics of saliva EVs sub-proteome of pSS patients compared to healthy controls (HC)

Methods: We included patients with a diagnosis of pSS made according to the AECG 2002 criteria and healthy volunteers as controls. Saliva was collected under standardized conditions. EVs were enriched by sequential ultracentrifugation steps from saliva samples. Peptide identification and quantitation was performed using a SWATH-MS approach using an assay spectral library for peptide matching. Protein-protein interaction network and pathway analysis were carried out to figure out the most representative biological paths in pSS.

Results: We enrolled 26 pSS patients (AECG 2002 criteria) and 13 healthy subjects. Quantitative data showed a distinct separation between pSS group and HC group, indicating that pSS may influence the phenotype of protein cargoes of salivary EVs. The majority of the differentially expressed proteins were found to be up-regulated in EVs pSS compared to controls. A highly interconnected sub-network of protein involved in several inflammatory processes was generated. Among several inflammatory pathways found in this study, a particular emphasis was given to proteins belonging to IL-12 signaling such as annexin A2, macrophage migration inhibitory factor (MIF), S100A8-A9 and plastin-2 proteins.

Conclusion: Our results highlight the key role of EVs S100 proteins and MIF as putative biomarkers for salivary gland dysfunction in pSS suggesting that the inflammatory phenotype observed in pSS whole saliva is also extended to salivary EVs.

Disclosure: C. Baldini, None; F. Finamore, None; F. Ferro, None; S. Rocchiccioli, None; M. Mosca, None; L. Mattii, None; A. Cecchettini, None.

To cite this abstract in AMA style:

Baldini C, Finamore F, Ferro F, Rocchiccioli S, Mosca M, Mattii L, Cecchettini A. Extracellular Vesicles in Primary Sjögren’s Syndrome: A Promising Source for Novel Proteomic Biomarkers [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/extracellular-vesicles-in-primary-sjogrens-syndrome-a-promising-source-for-novel-proteomic-biomarkers/. Accessed January 16, 2021.

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