Diagnostic Proteins Found in Patients with Sjögren's Syndrome

Sjögren's syndrome is accompanied by changes in the saliva composition, including changes in the acinar proteins.

In Sjögren's syndrome, an autoimmune disease, white blood cells attack the membranes and moisture-secreting glands of the mouth and eyes, leading to decreased production of saliva and tears. The eyes can itch, burn, or feel gritty and the mouth becomes dry, hindering speech, chewing, and swallowing and may lead to dental problems. Damage to the liver, kidneys, and lungs may also occur.

Dr. Laura Giusti and colleagues from the University of Pisa (Pisa, Italy) collected whole unstimulated saliva from a panel of 12 women diagnosed with primary Sjögren's syndrome and from 12 healthy women. Proteins were removed from the centrifuged liquids by mild acid precipitation and separated from each other using two-dimensional electrophoresis, with isoelectric focusing over a wide pH range (3-10) in the first dimension, followed by gel electrophoresis. After silver staining, the protein patterns from the patients were compared with those from the healthy control subjects by image analysis.

The proteins most affected by the disease were prolactin-inducible protein precursor (PIP), carbonic anhydrase VI, alpha-amylase, albumin, and cystatins. One major change was the total disappearance of carbonic anhydrase VI in the disease saliva. This enzyme converts salivary bicarbonate into carbon dioxide and water, a process that is essential for controlling the pH of saliva, and its loss appears to correlate with the reduction in pH value for Sjögren's syndrome patients.

The levels of several cystatins in patient saliva were also reduced, in some cases to zero. These proteins protect against proteinases by regulating proteolysis and tissue damage, and their altered expression might reflect the changing balance between proteinase and protease inhibitors, so affecting the function of the saliva. The observed reduction in PIP could be linked to long-term inflammation of the oral area.

Other proteins that appeared in the disease saliva that were absent in the control samples included cyclophilin and calgranulin B. The former has been associated with immune-mediated endothelial activation and dysfunction, whereas the latter is a calcium-binding protein that is present in cases of acute and chronic inflammation.

The scientists concluded that their work has proven the validity of proteomics in the study of Sjögren's syndrome, laying the foundations for its extension into the study of connective tissue disorders in general.


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