Biomarker profiles in serum and saliva of experimental Sjögren's syndrome: associations with specific autoimmune manifestations.
BACKGROUND
Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly targets the exocrine glands. The aim of this study was to investigate the involvement of 87 proteins measured in serum and 75 proteins analyzed in saliva in spontaneous experimental SS. In addition, we intended to compute a model of the immunological situation representing the overt disease stage of SS.


METHODS
Nondiabetic, nonobese diabetic (NOD) mice aged 21 weeks were evaluated for salivary gland function, salivary gland inflammation and extraglandular disease manifestations. The analytes, comprising chemokines, cytokines, growth factors, autoantibodies and other biomarkers, were quantified using multi-analyte profile technology and fluorescence-activated cell sorting. Age-matched and sex-matched Balb/c mice served as a reference.


RESULTS
We found NOD mice to exhibit impaired salivary flow, glandular inflammation and increased secretory SSB (anti-La) levels. Thirty-eight biomarkers in serum and 34 in saliva obtained from NOD mice were significantly different from those in Balb/c mice. Eighteen biomarkers in serum and three chemokines measured in saliva could predict strain membership with 80% to 100% accuracy. Factor analyses identified principal components mostly correlating with one clinical aspect of SS and having distinct associations with components extracted from other families of proteins.


CONCLUSIONS
Autoimmune manifestations of SS are greatly independent and associated with various immunological processes. However, CD40, CD40 ligand, IL-18, granulocyte chemotactic protein-2 and anti-muscarinic M3 receptor IgG3 may connect the different aspects of SS. Processes related to the adaptive immune system appear to promote SS with a strong involvement of T-helper-2 related proteins in hyposalivation. This approach further established saliva as an attractive biofluid for biomarker analyses in SS and provides a basis for the comparison and selection of potential drug targets and diagnostic markers.
Delaleu
Nicolas
N
Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Haukelandsveien, Bergen 5021, Norway. nicolas.delaleu@gades.uib.no
Immervoll
Heike
H
Cornelius
Janet
J
Jonsson
Roland
R
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000209:etiology*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005163:Factor Analysis, Statistical; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D012463:Saliva / Q000378:metabolism*; D012472:Salivation; D012793:Sialadenitis / Q000209:etiology; D012859:Sjogren's Syndrome / Q000097:blood / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology
D001323:Autoantibodies; D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D007074:Immunoglobulin G