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.
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.
Authors: Line Dam Heftdal; Thomas Andersen; Ditte Jæhger; Anders Woetmann; René Østgård; Elisabeth E Kenngott; Uta Syrbe; Joachim Sieper; Malene Hvid; Bent Deleuran; Tue W Kragstrup Journal: J Mol Med (Berl) Date: 2017-04-02 Impact factor: 4.599
Authors: James T Rosenbaum; Dongseok Choi; David J Wilson; Hans E Grossniklaus; Cailin H Sibley; Christina A Harrington; Stephen R Planck Journal: Exp Mol Pathol Date: 2015-01-14 Impact factor: 3.362
Authors: James T Rosenbaum; Dongseok Choi; David J Wilson; Hans E Grossniklaus; Christina A Harrington; Cailin H Sibley; Roger A Dailey; John D Ng; Eric A Steele; Craig N Czyz; Jill A Foster; David Tse; Chris Alabiad; Sander Dubovy; Prashant K Parekh; Gerald J Harris; Michael Kazim; Payal J Patel; Valerie A White; Peter J Dolman; Bobby S Korn; Don O Kikkawa; Deepak P Edward; Hind M Alkatan; Hailah al-Hussain; R Patrick Yeatts; Dinesh Selva; Patrick Stauffer; Stephen R Planck Journal: Exp Mol Pathol Date: 2015-07-08 Impact factor: 3.362
Authors: Marcel B M Teunissen; Nataliya G Yeremenko; Dominique L P Baeten; Saskia Chielie; Phyllis I Spuls; Menno A de Rie; Olivier Lantz; Pieter C M Res Journal: J Invest Dermatol Date: 2014-06-18 Impact factor: 8.551
Authors: James T Rosenbaum; Cailin H Sibley; Dongseok Choi; Christina A Harrington; Stephen R Planck Journal: Prog Retin Eye Res Date: 2015-12-01 Impact factor: 21.198
Authors: James T Rosenbaum; Dongseok Choi; Christina A Harrington; David J Wilson; Hans E Grossniklaus; Cailin H Sibley; Sherveen S Salek; John D Ng; Roger A Dailey; Eric A Steele; Brent Hayek; Caroline M Craven; Deepak P Edward; Azza M Y Maktabi; Hailah Al Hussain; Valerie A White; Peter J Dolman; Craig N Czyz; Jill A Foster; Gerald J Harris; Youn-Shen Bee; David T Tse; Chrisfouad R Alabiad; Sander R Dubovy; Michael Kazim; Dinesh Selva; R Patrick Yeatts; Bobby S Korn; Don O Kikkawa; Rona Z Silkiss; Jennifer A Sivak-Callcott; Patrick Stauffer; Stephen R Planck Journal: JAMA Ophthalmol Date: 2017-11-01 Impact factor: 7.389