By using quantitative two dimensional electrophoresis and matrix assisted laser desorption ionisation time of flight mass spectrometry, we identified 15 differently expressed proteins which apparently reflected kinase inhibitor Rucaparib the various histopathological aspects of pSS, from acinar loss, to lymphocytes infiltration, to local and systemic flogosis. At the time, the pattern of identified proteins was not preclinically validated. The aim of the current study was, therefore, to analyse by mass spectrometry techniques, coupled with Western blot and enzyme linked immunosorbent assay, the proteomic profile of pSS in an independent larger cohort of patients not only in comparison to healthy volunteers but Inhibitors,Modulators,Libraries also in comparison to pathologi cal controls.

Inhibitors,Modulators,Libraries To this purpose, we included subjects with non SS sicca syndrome which may provide Inhibitors,Modulators,Libraries a natural model of chronic dryness of the oral cavity not sus tained by an autoimmune response. Moreover, in order to verify whether salivary proteomics might be utilised to distinguish pSS from sSS the study was also extended to patients affected by SS and concomitant RA and SSc. The ultimate goal of this part of the study was, in other words, to support the work hypoth esis that proteomic analysis of whole saliva could represent a novel technique not only for the diagnosis of disorders involving salivary glands but also systemic autoimmune disorders even in the absence of any sali vary exocrinopathy. Finally, we also explored the biological and pathoge netic function of the detected putative discriminatory salivary proteomic biomarkers both in the local exocri nopathy and in the systemic inflammatory autoimmune systemic processes of pSS by employing the Ingenuity Pathway Analysis Knowledge base.

Materials and methods Study design This diagnostic case control study was subdivided into three different steps. The first exploratory phase was aimed at characterising the salivary proteomic profile of a large group of pSS subjects in comparison to healthy controls and pathological controls. The second Inhibitors,Modulators,Libraries chal lenge phase was aimed at preclinically validating Inhibitors,Modulators,Libraries by WB and ELISA the ability of these candidate biomarkers to differentiate pSS from healthy volunteers, subjects with non pSS sicca syndrome and patients with sSS. ELISA results were also correlated to the minor salivary gland focus score and to rheumatoid factor, anti Ro SSA and anti La SSB.

Finally, to investigate the biologi cal function of the significantly changing proteins, we applied the Ingenuity Pathway Analysis Knowl edge base. This platform enabled us to visualize the potential interactions between the identified biomarker signatures in saliva and other molecules inhibitor Pfizer of interest, which may not have been detected in this particular study, and to iden tify biological pathways underlying pSS disease process. The study was approved by the local Ethics Committee.