title: Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues.
abstract: OBJECTIVE
  To generate a molecular description of synovial tissue from rheumatoid arthritis (RA) patients that would allow us to unravel novel aspects of pathogenesis and to identify different forms of disease.
  
  
  METHODS
  We applied complementary DNA microarray analysis to profile gene expression, with a focus on immune-related genes, in affected joint tissues from RA patients and in tissues from osteoarthritis (OA) patients as a control. To validate microarray data, real-time polymerase chain reaction was performed on genes of interest.
  
  
  RESULTS
  The gene expression signatures of synovial tissues from RA patients showed considerable variability, resulting in the identification of at least two molecularly distinct forms of RA tissues. One class of tissues revealed abundant expression of clusters of genes indicative of an involvement of the adaptive immune response. Detailed analysis of the expression profile provided evidence for a prominent role of an activated signal transducer and activator of transcription 1 pathway in these tissues. The expression profiles of another group of RA tissues revealed an increased tissue remodeling activity and a low inflammatory gene expression signature. The gene expression pattern in the latter tissues was reminiscent of that observed in the majority of OA tissues.
  
  
  CONCLUSIONS
  The differences in the gene expression profiles provide a unique perspective for distinguishing different pathogenetic RA subsets based on molecular criteria. These data reflect important aspects of molecular variation that are relevant for understanding the biologic dysregulation underlying these subsets of RA. This approach may also help to define homogeneous groups for clinical studies and evaluation of targeted therapies.
authors.affiliation: Department of Molecular Cell Biology, VU Medical Center, van der Boechorst straat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: Tineke C T M
authors.initials: TC
authors.lastname: van der Pouw Kraan
authors.forename: Floris A
authors.initials: FA
authors.lastname: van Gaalen
authors.forename: Pia V
authors.initials: PV
authors.lastname: Kasperkovitz
authors.forename: Nicolette L
authors.initials: NL
authors.lastname: Verbeet
authors.forename: Tom J M
authors.initials: TJ
authors.lastname: Smeets
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Kraan
authors.forename: Mike
authors.initials: M
authors.lastname: Fero
authors.forename: Paul-Peter
authors.initials: PP
authors.lastname: Tak
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Elsbet
authors.initials: E
authors.lastname: Pieterman
authors.forename: Ferdinand C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: Ash A
authors.initials: AA
authors.lastname: Alizadeh
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Verweij
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D013583:Synovial Membrane / Q000378:metabolism / Q000503:physiopathology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators