Background/Purpose: S100 A proteins are multifunctional proteins expressed predominantly by myeloid cells, with a regulatory role in a variety of cellular processes including inflammation. Recently, serum and salivary S100A proteins have been described as increased in patients with primary Sjögren’s syndrome (pSS) with respect to healthy volunteers. In this study, we aimed at investigating whether salivary expression of S100 proteins may reflect different pSS disease phenotypes stratified on the basis of the complexity of minor salivary gland biopsies (MSGB) and on the impairment of unstimulated salivary flow rate (USFR).

Methods: Patients with pSS (AECG 2002) were included in this study at the diagnosis of the disease. Demographic and clinical data were collected prospectively as well as their USFR and MSGBs. A focus score (FS) ≥3 was considered as high and an USFR<2.5 ml/15’ was considered as low. Saliva samples were collected on ice, centrifuged and stored at -80°C. After removal of Albumin and IgG, a nano-HPLC system coupled with a Triple TOFTM 5600 mass spectrometer was used for the analysis of saliva proteomes of pSS patients. For the validation phase of the study, S100A7/psoriasin levels were determined by CircuLex S100A7/psoriasin ELISA kit (MBL International Corporation), according to manufacturer’s instructions.

Results: Fifteen pSS women were enrolled for the proteomic analysis: 5 with high FS and normal USFR, 5 with high FS and reduced USFR and 5 with low FS and reduced USFR. Among differentially expressed proteins, we found that S100 A2, 7, 8,9, 11 and 12 were significantly over-expressed in pSS with respect to controls. In details, S100 A7 levels were significantly increased in patients with higher FS and lower USFR with respect to the other two groups of patients; S100 A8 and A9 were increased in patients with higher FS and lower USFR only with respect to patients with high FS and normal USFR and S100 A 12 in patients with low FS and reduced USFR with respect to patients with high FS and normal USFR. We validated salivary expression of S100 A7 in 19 additional pSS patients and 8 controls confirming that S100A7 expression was significantly higher in patients with high FS and reduced USFR (305.6± 174 ng/ml vs 11±14 ng/ml vs 75.7±21.6 ng/ml, p=0.000).

Conclusion: Salivary S100 A proteins appeared as interesting novel potential biomarkers for the non-invasive stratification of homogenous subgroups of patients with pSS. ELISA results excellently mirrored proteomics and open the possibility to be clinically translated into routine diagnostic.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-and-validation-of-s100-salivary-proteins-as-putative-biomarkers-for-different-subsets-of-primary-sjogrens-syndrome-patients/