ARD: a large-scale analysis of longitudinal skin gene expression in systemic sclerosis

OBJECTIVE: Skin gene expression is dysregulated but heterogeneous in patients with systemic sclerosis (SSc) .
The relationship between clinical disease characteristics and skin gene expression is not fully established, and the extent to which skin gene expression changes in individuals over time is unknown .
The aim of this study was to determine the relationship between skin gene expression and clinical disease characteristics of SSc , as well as changes in skin gene expression over time .

OBJECTIVE: Skin gene expression is dysregulated but heterogeneous in patients with systemic sclerosis (SSc) .

The relationship between clinical disease characteristics and skin gene expression is not fully established, and the extent to which skin gene expression changes in individuals over time is unknown .
The aim of this study was to determine the relationship between skin gene expression and clinical disease characteristics of SSc , as well as changes in skin gene expression over time .

Methods: A total of 339 forearm skin biopsies were obtained from 113 SSc patients and 44 matched healthy controls .

A second biopsy was performed in 105 patients with SSc and a third biopsy was performed in 76 patients .
Global gene expression profiling was performed and differentially expressed genes and cell type-specific signatures in SSc were assessed in relation to the modified Rodnan skin score (mRSS) and other clinical variables .
Changes in skin gene expression over time were analyzed by mixed-effects model and principal component analysis .

Methods: A total of 339 forearm skin biopsies were obtained from 113 SSc patients and 44 matched healthy controls .
A second biopsy was performed in 105 patients with SSc and a third biopsy was performed in 76 patients .
Global gene expression profiling was performed and differentially expressed genes and cell type-specific signatures in SSc were assessed in relation to the modified Rodnan skin score (mRSS) and other clinical variables .
Changes in skin gene expression over time were analyzed by mixed-effects model and principal component analysis .
Immunohistochemical staining was performed to verify the conclusion .

     Results: Gene expression dysregulation was more severe in affected skin in patients with SSc than in patients with uninvolved skin .

Immune cell and fibroblast characteristics were positively correlated with mRSS .
High baseline immune cell and fibroblast characteristics predicted higher mRSS over time, but did not independently predict longitudinal mRSS after adjusting for baseline mRSS .
In early diffuse cutaneous SSc , immune cell and fibroblast characteristics declined over time, and overall skin gene expression normalized .
On immunohistochemical staining, most patients with early-stage diffuse cutaneous SSc with high baseline T cell and macrophage counts decreased these counts at follow-up .

     Results: Gene expression dysregulation was more severe in affected skin in patients with SSc than in patients with uninvolved skin .
Immune cell and fibroblast characteristics were positively correlated with mRSS .
High baseline immune cell and fibroblast characteristics predicted higher mRSS over time, but did not independently predict longitudinal mRSS after adjusting for baseline mRSS .
In early diffuse cutaneous SSc , immune cell and fibroblast characteristics declined over time, and overall skin gene expression normalized .
On immunohistochemical staining, most patients with early-stage diffuse cutaneous SSc with high baseline T cell and macrophage counts decreased these counts at follow-up .

     Conclusion: SSc skin thickness is associated with dysregulated gene expression in immune cells and fibroblasts
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In early diffuse SSc , skin gene expression changes over time and tends to normalize

     Conclusion: SSc skin thickness is associated with dysregulated gene expression in immune cells and fibroblasts

 

Source: Skaug B, Lyons MA, Swindell WR , et al .

Large-scale analysis of longitudinal skin gene expression in systemic sclerosis reveals relationships of immune cell and fibroblast activity with skin thickness and a trend towards normalisation over time.
Annals of the Rheumatic Diseases  2022; 81: 516-523.

Skaug B, Lyons MA, Swindell WR , et al .
Large-scale analysis of longitudinal skin gene expression in systemic sclerosis reveals relationships of immune cell and fibroblast activity with skin thickness and a trend towards normalisation over time.
Annals of the Rheumatic Diseases  2022; 81: 516-523.
, et al Annals of the Rheumatic Diseases  81: Comment here