Background Whole saliva is highly attractive for non invasive specimen collection. S100 proteins are calcium-binding proteins characterized by 2 calcium-binding EF (helix-loop-helix)-hand motifs connected by a central hinge region. In the extracellular compartment, S100A8 and S100A9 are known as damage-associated molecular pattern proteins because they are secreted by activated phagocytes during inflammatory processes. S100A8 and S100A9 induce a proinflammatory and thrombogenic response in endothelial cells, which is characterized by induction of proinflammatory cytokines and adhesion molecules such as VCAM-1 and ICAM-1, loss of cell-cell contacts and increased permeability of endothelium. Some members of the S100A protein family were found to be up-regulated in both saliva and tears of patients with Sjogren's Syndrome (SS).
Objectives To evaluate the salivary presence of S100A8 and S100A9 in patients with sicca syndrome and autoimmune diseases.
Methods S100A8 and S100A9 with its 2 isoforms (short and long) were studied using a proteomic approach in the saliva of 9 SS, 21 patients with connective tissue disease and sicca syndrome and 20 patients without sicca syndrome and with rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus and 16 healthy controls. The specimens were analyzed by HPLC coupled to electrospray-ionization mass spectrometry.
Results Variable expression of S100 protein family members (S100A8, S100A9) was detected in patients with autoimmune disease with and without sicca syndrome.S100A8 was detected in 6 (66.7%) patients in the group with SS, with a mean XIC peak area value of 4.5x108 ± 5.7x108 compared with 4 (25%) healthy subjects (mean XIC peak area 8.4x107 ± 2.2x106), 4 (19%) sicca syndrome patients (mean XIC peak area 3.8x107 ± 8.0x107), and only 1 (5%) patient with autoimmune disease without sicca syndrome (mean XIC peak area 5.7x107 ± 8.0x106). A statistically significant difference among the 4 groups in terms of frequency (P=0.003) and levels of detection (P=0.001) was found. S100A9 long isoform was detected in 7 (77.8%) patients in the group with SS, with a mean XIC peak area value of 5.9x108 ± 1.7x1010 compared with 6 (37.5%) healthy subjects (mean value of 1.9x107 ± 2.9x108) and 6 (28.6%) sicca syndrome patients (6.5x107 ± 1.4x108) and compared with 5 patients (25%) with autoimmune disease without sicca syndrome (2.4x107 ± 5.5x107). A statistically significant difference among the 4 groups in terms of frequency (p=0.04) and levels (p=0.004) was found. S100A9 short isofom was detected in 8 patients (88.9%) in the group with primary Sjogren's syndrome with mean levels of 1.11x109 ± 2.1x109, in 13 (65%) patients in the group with sicca syndrome (1.9x108 ± 2.5x108), in 7 patients (33.3%) with autoimmune disease (5.1x108 ± 1.1x108) and in 8 (50%) healthy controls (3.1x108 ± 3.5x108), with statistically significant differences in terms of frequency (p=0.03) and levels of detection (p<0.0001).
Conclusions The higher frequency and the increased level of S100 salivary proteins characterized patients with Sjogren's syndrome, while patients with sicca syndrome and autoimmune diseases presented increased frequency only of short isoform of S100A9.
Disclosure of Interest None declared
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