title: Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Abu N M
authors.initials: AN
authors.lastname: Nazmul-Hossain
authors.forename: Rodney P E
authors.initials: RP
authors.lastname: Pollard
authors.forename: Frans G M
authors.initials: FG
authors.lastname: Kroese
authors.forename: Arjan
authors.initials: A
authors.lastname: Vissink
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: Fred K L
authors.initials: FK
authors.lastname: Spijkervet
authors.forename: Hendrika
authors.initials: H
authors.lastname: Bootsma
authors.forename: Sara A
authors.initials: SA
authors.lastname: Michie
authors.forename: Sven U
authors.initials: SU
authors.lastname: Gorr
authors.forename: Ammon B
authors.initials: AB
authors.lastname: Peck
authors.forename: Chaochao
authors.initials: C
authors.lastname: Cai
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: David T W
authors.initials: DT
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010306:Parotid Gland / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D012859:Sjogren's Syndrome / Q000235:genetics*; D049490:Systems Biology / Q000379:methods