Progressive pulmonary sarcoidosis is associated with over-expression of TYK2 and p21Waf1/Cip1.
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.
Schischmanoff
Pierre Olivier
PO
Université Paris 13, UPRES-EA 3406, 93009 Bobigny, France. olivier.schischmanoff@avc.ap-hop-paris.fr
Naccache
Jean-Marc
JM
Carrere
Amélie
A
Richardson
Sylvia
S
Kambouchner
Marianne
M
Raphael
Martine
M
Valeyre
Dominique
D
Fagard
Remi
R
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
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D053634:TYK2 Kinase; C070139:TYK2 protein, human