Is GRP78/BiP a potential salivary biomarker in patients with rheumatoid arthritis?

Purpose: In the last few years, serum and joint synovial fluid have been extensively analyzed for the proteomic research of rheumatoid arthritis (RA) biomarkers. Nonetheless, to date, there have been no studies investigating salivary biomarkers in this condition. Therefore, aim of this study is to investigate the presence of potential biomarkers of RA in human whole saliva. Experimental design: We combined 2-DE and MS to analyze the whole saliva protein profile of 20 RA patients in comparison with 20 sex- and age-matched healthy subjects. Results: Eight salivary proteins resulted differentially expressed, namely calgranulin A, calgranulin B, apolipoprotein A-1, 6-phosphogluconate dehydrogenase, peroxiredoxin 5, epidermal fatty acid-binding protein, 78 kDa glucose-regulated protein precursor (GRP78/BiP), and 14-3-3 proteins. It is particularly interesting that chaperone GRP78/BiP showed the greatest increase in RA patients. This finding was validated by Western Blot analysis and the over-expression of GRP78/BiP appear to be distinctive of RA and drugs treatment independent. Conclusions and clinical relevance: This study provides a rationale for further studies aimed at evaluating any correlation between GRP78/BiP and different clinical/serological aspects of the disease in order to improve the diagnostic algorithms of RA.