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Media type:
E-Article
Title:
Skin Gene Expression Is Prognostic for the Trajectory of Skin Disease in Patients With Diffuse Cutaneous Systemic Sclerosis
Contributor:
Stifano, Giuseppina;
Sornasse, Thierry;
Rice, Lisa M.;
Na, Leo;
Chen‐Harris, Haiyin;
Khanna, Dinesh;
Jahreis, Angelika;
Zhang, Yuqing;
Siegel, Jeff;
Lafyatis, Robert
Published:
Wiley, 2018
Published in:
Arthritis & Rheumatology, 70 (2018) 6, Seite 912-919
Language:
English
DOI:
10.1002/art.40455
ISSN:
2326-5191;
2326-5205
Origination:
Footnote:
Description:
<jats:sec><jats:title>Objective</jats:title><jats:p>At present, there are no clinical or laboratory measures that accurately forecast the progression of skin fibrosis and organ involvement in patients with systemic sclerosis (<jats:styled-content style="fixed-case">SS</jats:styled-content>c). The goal of this study was to identify skin biomarkers that could be prognostic for the progression of skin fibrosis in patients with early diffuse cutaneous <jats:styled-content style="fixed-case">SS</jats:styled-content>c (dc<jats:styled-content style="fixed-case">SS</jats:styled-content>c).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We analyzed clinical data and gene expression in skin biopsy samples from 38 placebo‐treated patients, part of the Roche Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (<jats:styled-content style="fixed-case">FASSCINATE</jats:styled-content>) phase <jats:styled-content style="fixed-case">II</jats:styled-content> study of tocilizumab in <jats:styled-content style="fixed-case">SS</jats:styled-content>c. <jats:styled-content style="fixed-case">RNA</jats:styled-content> samples were analyzed using <jats:styled-content style="fixed-case">nC</jats:styled-content>ounter. A trajectory model based on a modified Rodnan skin thickness score was used to describe 3 skin disease trajectories over time. We examined the association of skin gene expression with skin score trajectory groups, by chi‐square test. Logistic regression was used to examine the prognostic power of each gene identified.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found that placebo‐treated patients with high expression of messenger <jats:styled-content style="fixed-case">RNA</jats:styled-content> for <jats:styled-content style="fixed-case">CD</jats:styled-content>14, <jats:styled-content style="fixed-case">SERPINE</jats:styled-content>1, <jats:styled-content style="fixed-case">IL</jats:styled-content>13<jats:styled-content style="fixed-case">RA</jats:styled-content>1, <jats:styled-content style="fixed-case">CTGF</jats:styled-content>, and <jats:styled-content style="fixed-case">OSMR</jats:styled-content> at baseline were more likely to have progressive skin score trajectories. We also found that those genes were prognostic for the risk of skin progression and that <jats:styled-content style="fixed-case">IL</jats:styled-content>13<jats:styled-content style="fixed-case">RA</jats:styled-content>1, <jats:styled-content style="fixed-case">OSMR</jats:styled-content>, and <jats:styled-content style="fixed-case">SERPINE</jats:styled-content>1 performed the best.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Skin gene expression of biomarkers associated with macrophages (<jats:styled-content style="fixed-case">CD</jats:styled-content>14, <jats:styled-content style="fixed-case">IL</jats:styled-content>13<jats:styled-content style="fixed-case">RA</jats:styled-content>1) and transforming growth factor β activation (<jats:styled-content style="fixed-case">SERPINE</jats:styled-content>1, <jats:styled-content style="fixed-case">CTGF</jats:styled-content>,<jats:styled-content style="fixed-case"> OSMR</jats:styled-content>) are prognostic for progressive skin disease in patients with dc<jats:styled-content style="fixed-case">SS</jats:styled-content>c. These biomarkers may provide guidance in decision‐making about which patients should be considered for aggressive therapies and/or for clinical trials.</jats:p></jats:sec>