Salivary proteomic and genomic biomarkers for primary Sjögren's syndrome.
OBJECTIVE
To identify a panel of protein and messenger RNA (mRNA) biomarkers in human whole saliva (WS) that may be used in the detection of primary Sjögren's syndrome (SS).


METHODS
Mass spectrometry and expression microarray profiling were used to identify candidate protein and mRNA biomarkers of primary SS in WS samples. Validation of the discovered mRNA and protein biomarkers was also demonstrated using real-time quantitative polymerase chain reaction and immunoblotting techniques.


RESULTS
Sixteen WS proteins were found to be down-regulated and 25 WS proteins were found to be up-regulated in primary SS patients compared with matched healthy control subjects. These proteins reflected the damage of glandular cells and inflammation of the oral cavity system in patients with primary SS. In addition, 16 WS peptides (10 up-regulated and 6 down-regulated in primary SS) were found at significantly different levels (P < 0.05) in primary SS patients and controls. Using stringent criteria (3-fold change; P < 0.0005), 27 mRNA in saliva samples were found to be significantly up-regulated in the primary SS patients. Strikingly, 19 of 27 genes that were found to be overexpressed were interferon-inducible or were related to lymphocyte filtration and antigen presentation known to be involved in the pathogenesis of primary SS.


CONCLUSIONS
Our preliminary study has indicated that WS from patients with primary SS contains molecular signatures that reflect damaged glandular cells and an activated immune response in this autoimmune disease. These candidate proteomic and genomic biomarkers may improve the clinical detection of primary SS once they have been further validated. We also found that WS contains more informative proteins, peptides, and mRNA, as compared with gland-specific saliva, that can be used in generating candidate biomarkers for the detection of primary SS.
Hu
Shen
S
University of California, Los Angeles, California, USA.
Wang
Jianghua
J
Meijer
Jiska
J
Ieong
Sonya
S
Xie
Yongming
Y
Yu
Tianwei
T
Zhou
Hui
H
Henry
Sharon
S
Vissink
Arjan
A
Pijpe
Justin
J
Kallenberg
Cees
C
Elashoff
David
D
Loo
Joseph A
JA
Wong
David T
DT
D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D023281:Genomics; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D012463:Saliva / Q000378:metabolism*; D012680:Sensitivity and Specificity; D012859:Sjogren's Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D012333:RNA, Messenger