PURPOSE OF REVIEW: The purpose of this study is to review recent hypothesis-driven studies that utilize global gene expression data for elucidating the molecular basis of systemic sclerosis (SSc) and its various clinical manifestations. RECENT FINDINGS: The longitudinal skin gene expression studies indicate that the previously identified molecular subsets are stable over time and might identify inherent subgroups of SSc patients. Skin transcript follow-up studies indicate that the Wnt/β-catenin pathway plays an important role in promotion of fibrogenesis in fibroblasts and preadipocytes. Furthermore, the transcript profile of sclerodermatous graft-versus-host disease (sclGVHD) mice resembles the skin transcriptomes of a subgroup of SSc patientswith IL13/IL4-inducible skin signature wherein the profibrotic chemokine CCL2 plays a key role. The comparison of skin biopsies from SSc patients to skin lesions of patients with cutaneous lupus and dermatomyositis has provided valuable information about the interferon (IFN) signature in these autoimmune diseases. Furthermore, plasma IFN-inducible chemokines correlate with the IFN gene expression score in SSc patients, enabling researchers to examine this molecular signature in large SSc cohorts with serum or plasma collection. SUMMARY: Global gene expression profiling in skin and peripheral blood can contribute to a better understanding of SSc pathogenesis and identify novel biomarkers and therapeutic targets.
PURPOSE OF REVIEW: The purpose of this study is to review recent hypothesis-driven studies that utilize global gene expression data for elucidating the molecular basis of systemic sclerosis (SSc) and its various clinical manifestations. RECENT FINDINGS: The longitudinal skin gene expression studies indicate that the previously identified molecular subsets are stable over time and might identify inherent subgroups of SSc patients. Skin transcript follow-up studies indicate that the Wnt/β-catenin pathway plays an important role in promotion of fibrogenesis in fibroblasts and preadipocytes. Furthermore, the transcript profile of sclerodermatous graft-versus-host disease (sclGVHD) mice resembles the skin transcriptomes of a subgroup of SSc patientswith IL13/IL4-inducible skin signature wherein the profibrotic chemokine CCL2 plays a key role. The comparison of skin biopsies from SSc patients to skin lesions of patients with cutaneous lupus and dermatomyositis has provided valuable information about the interferon (IFN) signature in these autoimmune diseases. Furthermore, plasma IFN-inducible chemokines correlate with the IFN gene expression score in SSc patients, enabling researchers to examine this molecular signature in large SSc cohorts with serum or plasma collection. SUMMARY: Global gene expression profiling in skin and peripheral blood can contribute to a better understanding of SSc pathogenesis and identify novel biomarkers and therapeutic targets.
Authors: Humphrey Gardner; Jeffrey R Shearstone; Raj Bandaru; Tom Crowell; Matthew Lynes; Maria Trojanowska; Jaspreet Pannu; Edwin Smith; Stefania Jablonska; Maria Blaszczyk; Filemon K Tan; Maureen D Mayes Journal: Arthritis Rheum Date: 2006-06
Authors: Romy B Christmann; Everett Hayes; Sarah Pendergrass; Cristina Padilla; Giuseppina Farina; Alsya J Affandi; Michael L Whitfield; Harrison W Farber; Robert Lafyatis Journal: Arthritis Rheum Date: 2011-06
Authors: Jun Wei; Asish K Ghosh; Jennifer L Sargent; Kazuhiro Komura; Minghua Wu; Qi-Quan Huang; Manu Jain; Michael L Whitfield; Carol Feghali-Bostwick; John Varga Journal: PLoS One Date: 2010-11-02 Impact factor: 3.240
Authors: Michael L Whitfield; Deborah R Finlay; John Isaac Murray; Olga G Troyanskaya; Jen-Tsan Chi; Alexander Pergamenschikov; Timothy H McCalmont; Patrick O Brown; David Botstein; M Kari Connolly Journal: Proc Natl Acad Sci U S A Date: 2003-10-06 Impact factor: 11.205
Authors: Kerry M Leehan; Nathan P Pezant; Astrid Rasmussen; Kiely Grundahl; Jacen S Moore; Lida Radfar; David M Lewis; Donald U Stone; Christopher J Lessard; Nelson L Rhodus; Barbara M Segal; R Hal Scofield; Kathy L Sivils; Courtney Montgomery; A Darise Farris Journal: Clin Exp Rheumatol Date: 2017-10-23 Impact factor: 4.473
Authors: Brian Skaug; Dinesh Khanna; William R Swindell; Monique E Hinchcliff; Tracy M Frech; Virginia D Steen; Faye N Hant; Jessica K Gordon; Ami A Shah; Lisha Zhu; W Jim Zheng; Jeffrey L Browning; Alexander M S Barron; Minghua Wu; Sudha Visvanathan; Patrick Baum; Jennifer M Franks; Michael L Whitfield; Victoria K Shanmugam; Robyn T Domsic; Flavia V Castelino; Elana J Bernstein; Nancy Wareing; Marka A Lyons; Jun Ying; Julio Charles; Maureen D Mayes; Shervin Assassi Journal: Ann Rheum Dis Date: 2019-11-25 Impact factor: 19.103