title: Progressive pulmonary sarcoidosis is associated with over-expression of TYK2 and p21Waf1/Cip1.
abstract: OBJECTIVE
  Sarcoidosis is a multisystemic disorder of unknown aetiology with diverse clinical phenotypes characterised by granulomatous formation in involved organs. The factors controlling the evolution of pulmonary involvement -- a major point in the progression of sarcoidosis -- are poorly understood. The aim of our study was to identify alterations of gene expression associated with the progression of the granulomatous process in pulmonary sarcoidosis.
  
  
  METHODS
  Using microarray analysis, we compared the gene expression profiles of bronchoalveolar lavage cells in three patients with progressive pulmonary sarcoidosis and in three patients with stable pulmonary sarcoidosis. Microarrays data were analysed using a non-parametric method that estimates the False positive Detection Rate for chosen thresholds of differential expression (software SAM, Significance Analysis of Microarrays). We further controlled the expression of three selected genes by semi-quantitative RT-PCR experiments.
  
  
  RESULTS
  Fourteen genes were found significantly upregulated in the cases with progressive sarcoidosis including three genes coding for effectors of the Th1 immune response: the protein tyrosine kinase TYK2, the Interferon-gamma receptor 2 and the cell cycle inhibitor p21Waf1/Cip1. Semi-quantitative RT-PCR confirmed the increased expression of TYK2 and p21Waf1/Cip1, but not of the Interferon-gamma receptor 2.
  
  
  CONCLUSIONS
  Our results confirm the feasibility of microarrays analysis in bronchoalveolar lavage, cells and are consistent with an involvement of p21Waf1/Cip1 and TYK2, two components of the Th1-inflammatory response pathway, in the progression of pulmonary sarcoidosis.
authors.affiliation: Université Paris 13, UPRES-EA 3406, 93009 Bobigny, France. olivier.schischmanoff@avc.ap-hop-paris.fr
authors.forename: Pierre Olivier
authors.initials: PO
authors.lastname: Schischmanoff
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Naccache
authors.forename: Amélie
authors.initials: A
authors.lastname: Carrere
authors.forename: Sylvia
authors.initials: S
authors.lastname: Richardson
authors.forename: Marianne
authors.initials: M
authors.lastname: Kambouchner
authors.forename: Martine
authors.initials: M
authors.lastname: Raphael
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.forename: Remi
authors.initials: R
authors.lastname: Fagard
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D013902:Radiography, Thoracic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017565:Sarcoidosis, Pulmonary / Q000175:diagnosis / Q000235:genetics*; D053634:TYK2 Kinase / Q000096:biosynthesis / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D053634:TYK2 Kinase; C070139:TYK2 protein, human