Details

Autor(en) / Beteiligte

• Skaug, Brian
• Khanna, Dinesh
• Swindell, William R
• Hinchcliff, Monique E
• Frech, Tracy M
• Steen, Virginia D
• Hant, Faye N
• Gordon, Jessica K
• Shah, Ami A
• Zhu, Lisha
• Zheng, W Jim
• Browning, Jeffrey L
• Barron, Alexander M S
• Wu, Minghua
• Visvanathan, Sudha
• Baum, Patrick
• Franks, Jennifer M
• Whitfield, Michael L
• Shanmugam, Victoria K
• Domsic, Robyn T
• Castelino, Flavia V
• Bernstein, Elana J
• Wareing, Nancy
• Lyons, Marka A
• Ying, Jun
• Charles, Julio
• Mayes, Maureen D
• Assassi, Shervin

Titel

Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile

Ist Teil von

• Annals of the rheumatic diseases, 2020-03, Vol.79 (3), p.379-386

Ort / Verlag

England: BMJ Publishing Group LTD

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• ObjectivesDetermine global skin transcriptome patterns of early diffuse systemic sclerosis (SSc) and how they differ from later disease.MethodsSkin biopsy RNA from 48 patients in the Prospective Registry for Early Systemic Sclerosis (PRESS) cohort (mean disease duration 1.3 years) and 33 matched healthy controls was examined by next-generation RNA sequencing. Data were analysed for cell type-specific signatures and compared with similarly obtained data from 55 previously biopsied patients in Genetics versus Environment in Scleroderma Outcomes Study cohort with longer disease duration (mean 7.4 years) and their matched controls. Correlations with histological features and clinical course were also evaluated.ResultsSSc patients in PRESS had a high prevalence of M2 (96%) and M1 (94%) macrophage and CD8 T cell (65%), CD4 T cell (60%) and B cell (69%) signatures. Immunohistochemical staining of immune cell markers correlated with the gene expression-based immune cell signatures. The prevalence of immune cell signatures in early diffuse SSc patients was higher than in patients with longer disease duration. In the multivariable model, adaptive immune cell signatures were significantly associated with shorter disease duration, while fibroblast and macrophage cell type signatures were associated with higher modified Rodnan Skin Score (mRSS). Immune cell signatures also correlated with skin thickness progression rate prior to biopsy, but did not predict subsequent mRSS progression.ConclusionsSkin in early diffuse SSc has prominent innate and adaptive immune cell signatures. As a prominently affected end organ, these signatures reflect the preceding rate of disease progression. These findings could have implications in understanding SSc pathogenesis and clinical trial design.