Abstract
ObjectivesTo determine the diagnostic potential of simultaneous presence of serum anti-SSA/Ro and upregulated salivary protein biomarkers in patients with primary Sjögren’s syndrome (pSS).MethodsPrevious proteomics data on the intensity of neutrophil elastase, calreticulin, tripartite motif containing protein 29 (TRIM29), clusterin and vitronectin provided basis for performing extended analysis. Protein data was obtained by liquid chromatography tandem mass spectrometry technique in whole saliva from 24 patients with pSS and 16 patients having symptoms of pSS, but not fulfilling the American College of Rheumatology/European League against Rheumatism classification criteria (non-pSS). Serum anti-SSA/Ro antibody was measured using enzyme-linked immunosorbent assays. Receiver operating characteristic curve (ROC) value was calculated for combined biomarkers.ResultsSimultaneous presence of serum anti-SSA/Ro and upregulated salivary TRIM29 provided the most optimal combination with an area under curve (AUC) of 0.995 (95% CI 0.98–1.00, p = 2.0E-7 and standard error 0.007) and combinations of sensitivity and specificity within the interval of 91–100%. ROC analysis showed that salivary levels of TRIM29 alone enabled differentiation between pSS and non-pSS with an area under curve (AUC) of 0.88 (95%CI 0.77–1.00). All patients with pSS and 3 non-pSS patients were serum anti-SSA/Ro positive.ConclusionsSimultaneous presence of serum anti-SSA/Ro and upregulated salivary TRIM29 provided a high diagnostic accuracy exceeding that of currently available tools used in pSS diagnostics. This biomarker combination represents a promising less invasive diagnostic tool for pSS. The clinical applicability of TRIM29 needs further testing in independent cohorts using relevant analytical techniques.
Highlights
Primary Sjogren’s syndrome is an autoimmune disease characterized by immune-mediated inflammation directed by the exocrine glands
Simultaneous presence of serum anti-SSA/Ro and upregulated salivary tripartite motif containing protein 29 (TRIM29) provided a high diagnostic accuracy exceeding that of currently available tools used in Primary Sjogren’s syndrome (pSS) diagnostics
TRIM21 is part of the TRIM-protein family, whereas most of the TRIM proteins are induced by interferons, which are signaling molecules considered to play a crucial role in the initial phases of the pathogenesis of pSS [6]
Summary
Primary Sjogren’s syndrome (pSS) is an autoimmune disease characterized by immune-mediated inflammation directed by the exocrine glands. Anti-SSA/Ro antibodies may be present in other inflammatory rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, primary biliary cirrhosis and myositis [3,4]. In a recently published study of ours, we identified a panel of upregulated salivary proteins including neutrophil elastase, calreticulin, TRIM29, clusterin and vitronectin [8]. Among this panel of potential protein biomarker candidates, additional statistical analyses presented in this brief report shows that upregulated TRIM29 seems to represent a remarkably good marker for pSS when combined with presence of anti-SSA/Ro in serum. Dysregulated TRIM29 has not previously been associated to pSS, it is noteworthy that this particular protein is part of the same protein family as TRIM21 (SSA/Ro52), and may share important features and biological roles in the pathogenesis of pSS
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