Disease-specific and inflammation-independent stromal alterations in spondylarthritis synovitis
Nataliya Yeremenko
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Drs. Yeremenko, Tak, and Baeten are coinventors on patent P88989EP00 for methods of typing samples for rheumatoid arthritis and spondylarthritis so as to discriminate between the two conditions in early disease, as well as sets of genes for use in this method and a nucleotide microarray.
Search for more papers by this authorTroy Noordenbos
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorTineke Cantaert
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Yale University School of Medicine, New Haven, Connecticut
Search for more papers by this authorMelissa van Tok
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorMarleen van de Sande
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorJuan D. Cañete
Hospital Clinic de Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Search for more papers by this authorPaul P. Tak
Academic Medical Center, University of Amsterdam, and Arthrogen BV, Amsterdam, The Netherlands
GlaxoSmithKline, Stevenage, UK
Drs. Yeremenko, Tak, and Baeten are coinventors on patent P88989EP00 for methods of typing samples for rheumatoid arthritis and spondylarthritis so as to discriminate between the two conditions in early disease, as well as sets of genes for use in this method and a nucleotide microarray.
Search for more papers by this authorCorresponding Author
Dominique Baeten
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Drs. Yeremenko, Tak, and Baeten are coinventors on patent P88989EP00 for methods of typing samples for rheumatoid arthritis and spondylarthritis so as to discriminate between the two conditions in early disease, as well as sets of genes for use in this method and a nucleotide microarray.
Department of Clinical Immunology and Rheumatology, F4-105, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorNataliya Yeremenko
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Drs. Yeremenko, Tak, and Baeten are coinventors on patent P88989EP00 for methods of typing samples for rheumatoid arthritis and spondylarthritis so as to discriminate between the two conditions in early disease, as well as sets of genes for use in this method and a nucleotide microarray.
Search for more papers by this authorTroy Noordenbos
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorTineke Cantaert
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Yale University School of Medicine, New Haven, Connecticut
Search for more papers by this authorMelissa van Tok
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorMarleen van de Sande
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorJuan D. Cañete
Hospital Clinic de Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Search for more papers by this authorPaul P. Tak
Academic Medical Center, University of Amsterdam, and Arthrogen BV, Amsterdam, The Netherlands
GlaxoSmithKline, Stevenage, UK
Drs. Yeremenko, Tak, and Baeten are coinventors on patent P88989EP00 for methods of typing samples for rheumatoid arthritis and spondylarthritis so as to discriminate between the two conditions in early disease, as well as sets of genes for use in this method and a nucleotide microarray.
Search for more papers by this authorCorresponding Author
Dominique Baeten
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands
Drs. Yeremenko, Tak, and Baeten are coinventors on patent P88989EP00 for methods of typing samples for rheumatoid arthritis and spondylarthritis so as to discriminate between the two conditions in early disease, as well as sets of genes for use in this method and a nucleotide microarray.
Department of Clinical Immunology and Rheumatology, F4-105, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorAbstract
Objective
The molecular processes driving the distinct patterns of synovial inflammation and tissue remodeling in spondylarthritis (SpA) as compared to rheumatoid arthritis (RA) remain largely unknown. Therefore, we aimed to identify novel and unsuspected disease-specific pathways in SpA by a systematic and unbiased synovial gene expression analysis.
Methods
Differentially expressed genes were identified by pan-genomic microarray and confirmed by quantitative polymerase chain reaction and immunohistochemical analyses of synovial tissue biopsy samples from patients with SpA (n = 63), RA (n = 28), and gout (n = 9). The effect of inflammation on gene expression was assessed by stimulating fibroblast-like synoviocytes (FLS) with synovial fluid and by analysis of synovial tissue samples at weeks 0 and 12 of etanercept treatment.
Results
Using very stringent statistical thresholds, microarray analysis identified 64 up-regulated transcripts in patients with SpA synovitis as compared to those with RA synovitis. Pathway analysis revealed a robust myogene signature in this gene set. The myogene signature was technically and biologically reproducible, was specific for SpA, and was independent of disease duration, treatment, and SpA subtype (nonpsoriatic versus psoriatic). Synovial tissue staining identified the myogene expressing cells as vimentin-positive, prolyl 4-hydroxylase β–positive, CD90+, and CD146+ mesenchymal cells that were significantly overrepresented in the intimal lining layer and synovial sublining of inflamed SpA synovium. Neither in vitro exposure to synovial fluid from inflamed SpA joints nor in vivo blockade of tumor necrosis factor modulated the SpA-specific myogene signature.
Conclusion
These data identify a novel and disease-specific myogene signature in SpA synovitis. The fact that this stromal alteration appeared not to be downstream of local inflammation warrants further analysis of its functional role in the pathogenesis of the disease.
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