Session Title: Genetics and Genomics of Rheumatic Disease II
Session Type: Abstract Submissions (ACR)
Background/Purpose: Nowadays, the advances of novel proteomic technologies are encouraging research projects for generating reliable diagnostic biomarkers for primary Sjögren’s syndrome (pSS) to be used in both clinical settings and in clinical trials. Aim of this study was to identify the most significant salivary biomarkers in pSS using proteomic methods and to correlate pSS patients’ salivary proteomic profile to the different histological and immunological aspects of the disease.
Methods: Salivary samples from patients affected by pSS, and sex- and age-matched healthy volunteers (HC) were consecutively collected from May 2012 to February 2013. The ProteinChip System, Series 4000 Personal Edition (Ciphergen Biosystems, Inc) was used to perform SELDI-TOF-MS. The cation exchange array CM10 (Bio-Rad) was selected. Chips were read on a Ciphergen Express Data Manager – Personal Edition (version 3.5). SELDI-TOF-MS data were analyzed by using Mann-Whitney non-parametric test for univariate analysis coupled with a classification and regression tree (CART) algorithm in the multivariate setting. Only significant variables (p<0.05) at the univariate analysis were included in the CART algorithm.
Results: Unstimulated whole saliva samples were collected from 72 consecutive unselected female patients with pSS and from 29 sex- and age- matched HC. A total of 75 peaks were detected at the SELDI-TOF-MS. We found that 25 peaks were significantly different in the pSS patient group with respect to HC (P<0.05). Among these 25 peaks, the selected CART tree indentified 7149 m/z , 7192 m/z, 13507 m/z, 13714 m/z, 16547 m/z, 24059 m/z as best independent biomarkers able to discriminate between pSS and HC with a sensitivity of 96%, a specificity of 70% and a global cross validated error of 29%. Peaks of 7192 m/z, 24059 m/z and two further peaks of 28674 m/z and 33285 m/z were also significantly different in the group of pSS patients with parenchymal inhomogenicity at the salivary gland ultrasonography. Furthermore, in pSS patients with high focus score at the minor salivary gland biopsy and in pSS patients positive for anti-Ro/SSA antibodies, peaks of 4205 m/z and 22232 m/z and peaks of 3502 m/z and 4808 m/z were differently expressed, respectively.
Conclusion: This study supports the use of high throughput technologies to approach the challenge of the discovery of new, accurate diagnostic biomarkers for pSS and its clinical subsets.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mass-spectrometry-based-salivary-proteomics-for-the-discovery-of-novel-diagnostic-biomarkers-for-primary-sjogrens-syndrome-and-its-clinical-subsets/