Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus.
OBJECTIVE
Synovitis is a common feature of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but the pattern of joint involvement differs in each disease. This study was undertaken to investigate the global gene expression profiles in synovial biopsy tissue from the swollen knees of untreated SLE patients (n = 6), RA patients (n = 7), and osteoarthritis (OA) patients (n = 6).


METHODS
Synovial biopsy samples were obtained from the affected knees of patients in the 3 groups by needle arthroscopy. Half of the material was used for extraction of total RNA, amplification of complementary RNA, and high-density oligonucleotide spotted hybridization arrays. On the remaining tissue samples, real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical experiments were performed to confirm the microarray data.


RESULTS
SLE synovial biopsy tissue displayed a significant down-regulation of genes involved in extracellular matrix (ECM) homeostasis and a significant up-regulation of interferon-inducible (IFI) genes. Real-time RT-PCR experiments confirmed the up-regulation of selected IFI genes (IFI27, IFI44, and IFI44L) in the SLE synovial tissue. Immunohistochemical analyses showed that 3 molecules involved in ECM regulation, chondroitin sulfate proteoglycan 2, latent transforming growth factor beta binding protein 2, and fibroblast activation protein alpha, were significantly down-regulated in SLE synovium. In contrast, immunostaining for IFI27, Toll-like receptor 4, and STAT-1 resulted in higher quantitative scores in SLE synovial tissue, which could be attributed to the fact that the RA samples had a large population of inflammatory cell infiltrates that were negative for these markers.


CONCLUSIONS
Arthritis in SLE has a very distinct molecular signature as compared with that in OA and RA, characterized by up-regulation of IFI genes and down-regulation of genes involved in ECM homeostasis.
Nzeusseu Toukap
A
A
Université catholique de Louvain, Brussels, Belgium.
Galant
C
C
Theate
I
I
Maudoux
A L
AL
Lories
R J U
RJ
Houssiau
F A
FA
Lauwerys
B R
BR
D000328:Adult; D000368:Aged; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases; D020869:Gene Expression Profiling; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D053675:Versicans / Q000235:genetics / Q000378:metabolism; D000099167:Fibroblast Activation Protein Alpha
D000941:Antigens; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D010450:Endopeptidases; D018093:Gelatinases; D053779:Latent TGF-beta Binding Proteins; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D053675:Versicans; D000099167:Fibroblast Activation Protein Alpha; C406887:IFI27 protein, human; C065888:IFI44 protein, human; C509035:LTBP2 protein, human; C508322:VCAN protein, human