Dr. Wong has stock ownership or options in RNAmeTRIX.
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Sjögren's Syndrome
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Preclinical validation of salivary biomarkers for primary Sjögren's syndrome
Article first published online: 8 JUL 2010
DOI: 10.1002/acr.20289
Copyright © 2010 by the American College of Rheumatology
Additional Information
How to Cite
Hu, S., Gao, K., Pollard, R., Arellano-Garcia, M., Zhou, H., Zhang, L., Elashoff, D., Kallenberg, C. G. M., Vissink, A. and Wong, D. T. (2010), Preclinical validation of salivary biomarkers for primary Sjögren's syndrome. Arthritis Care & Research, 62: 1633–1638. doi: 10.1002/acr.20289
Publication History
- Issue published online: 2 NOV 2010
- Article first published online: 8 JUL 2010
- Manuscript Accepted: 28 JUN 2010
- Manuscript Received: 21 DEC 2009
Funded by
- USPHS. Grant Number: R01-DE017593
Abstract
Objective
Sjögren's syndrome (SS) is a systemic autoimmune disease with a variety of presenting symptoms that may delay its diagnosis. We previously discovered a number of candidate salivary biomarkers for primary SS using both mass spectrometry and expression microarray analysis. In the current study, we aimed to verify these candidate biomarkers in independent patient populations and to evaluate their predictive values for primary SS detection.
Methods
In total, 34 patients with primary SS, 34 patients with systemic lupus erythematosus (SLE), and 34 healthy individuals were enrolled for the validation studies. Salivary protein biomarkers were measured using either Western blotting or enzyme-linked immunosorbent assay, and the messenger RNA (mRNA) biomarkers were measured using quantitative polymerase chain reaction. Statistical analysis was performed using R software, version 2.9.
Results
Three protein biomarkers (cathepsin D [CPD], α-enolase, and β2-microglobulin [β2m]) and 3 mRNA biomarkers (myeloid cell nuclear differentiation antigen [MNDA], guanylate binding protein 2 [GBP-2], and low-affinity IIIb receptor for the Fc fragment of IgG) were significantly elevated in patients with primary SS compared with both SLE patients and healthy controls. The combination of 3 protein biomarkers, CPD, α-enolase, and β2m, yielded a receiver operating characteristic (ROC) value of 0.99 in distinguishing primary SS from healthy controls. The combination of protein biomarkers β2m and 2 mRNA biomarkers, MNDA and GBP-2, reached an ROC of 0.95 in discriminating primary SS from SLE.
Conclusion
We have successfully verified a panel of protein and mRNA biomarkers that can discriminate primary SS from both SLE and healthy controls. If further validated in patients with primary SS and those with sicca symptoms but no autoimmune disease, these biomarkers may lead to a simple yet highly discriminatory clinical tool for diagnosis of primary SS.