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Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model

Steve Horvath1, Abu NM Nazmul-Hossain1, Rodney PE Pollard2, Frans GM Kroese2, Arjan Vissink2, Cees GM Kallenberg2, Fred KL Spijkervet2, Hendrika Bootsma2, Sara A Michie3, Sven U Gorr4, Ammon B Peck5, Chaochao Cai1, Hui Zhou1 and David TW Wong1*

  • * Corresponding author: David TW Wong

  • † Equal contributors

Author affiliations

1 School of Dentistry, Dental Research Institute, University of California at Los Angeles, 10833 Le Conte Avenue, 73-017 CHS, Los Angeles, CA 90095-1668, USA

2 Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, Groningen, the Netherlands

3 School of Medicine, Stanford University, 300 Pasteur Drive, R241 MC 5324, Stanford, CA 94305, USA

4 School of Dentistry, University of Minnesota, 7536 Moos HST, 515 Delaware Street SE, Minneapolis, MN 55455, USA

5 Department of Pathology, Immunology and Laboratory Medicine, School of Medicine, University of Florida College of Medicine, JHMHSC D6-33D, 1600 SW Archer Road, Gainesville, FL 32610-0275, USA

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Citation and License

Arthritis Research & Therapy 2012, 14:R238  doi:10.1186/ar4081

Published: 1 November 2012



Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Despite extensive studies to understand the disease process utilizing human and mouse models, the intersection between these species remains elusive. To address this gap, we utilized a novel systems biology approach to identify disease-related gene modules and signaling pathways that overlap between humans and mice.


Parotid gland tissues were harvested from 24 pSS and 16 non-pSS sicca patients and 25 controls. For mouse studies, salivary glands were harvested from C57BL/6.NOD-Aec1Aec2 mice at various times during development of pSS-like disease. RNA was analyzed with Affymetrix HG U133+2.0 arrays for human samples and with MOE430+2.0 arrays for mouse samples. The images were processed with Affymetrix software. Weighted-gene co-expression network analysis was used to identify disease-related and functional pathways.


Nineteen co-expression modules were identified in human parotid tissue, of which four were significantly upregulated and three were downregulated in pSS patients compared with non-pSS sicca patients and controls. Notably, one of the human disease-related modules was highly preserved in the mouse model, and was enriched with genes involved in immune and inflammatory responses. Further comparison between these two species led to the identification of genes associated with leukocyte recruitment and germinal center formation.


Our systems biology analysis of genome-wide expression data from salivary gland tissue of pSS patients and from a pSS mouse model identified common dysregulated biological pathways and molecular targets underlying critical molecular alterations in pSS pathogenesis.