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.
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.
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DOI：
10.1136/annrheumdis-2021-221352
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发表时间：
2022-04
影响因子：
27.4
通讯作者：
Assassi S
中科院分区：
文献类型：
--
作者：
Skaug B;Lyons MA;Swindell WR;Salazar GA;Wu M;Tran TM;Charles J;Vershel CP;Mayes MD;Assassi S
确定皮肤基因表达与系统性硬化症 (SSc) 临床疾病特征之间的关系，以及皮肤基因表达随时间的变化。从 113 名 SSc 患者和 44 名匹配的健康对照中总共获得了 339 份前臂皮肤活检样本。 105 名 SSc 患者进行了第二次活检，76 名患者进行了第三次活检。进行了全局基因表达谱分析，并评估了 SSc 中差异表达的基因和细胞类型特异性特征与 mRSS 和其他临床变量的关系。通过混合效应模型和主成分分析分析皮肤基因表达随时间的变化。进行免疫组织化学染色以验证结论。皮肤受影响的 SSc 患者的基因表达失调比皮肤未受影响的患者更严重。免疫细胞和成纤维细胞特征与 mRSS 呈正相关。高基线免疫细胞和成纤维细胞特征随着时间的推移预测更高的 mRSS，但在调整基线 mRSS 后不能独立预测纵向 mRSS。在早期弥漫性皮肤 SSc 中，免疫细胞和成纤维细胞特征随着时间的推移而下降，总体皮肤基因表达趋于正常化。在免疫组织化学染色中，大多数具有高基线 T 细胞和巨噬细胞数量的早期弥漫性皮肤 SSc 患者在随访时这些数量有所下降。 SSc 的皮肤厚度与免疫细胞和成纤维细胞基因表达失调有关。早期弥漫性 SSc 中皮肤基因表达随时间变化，并有趋于正常化的趋势。这些观察结果与了解 SSc 发病机制相关，并可为治疗策略和临床试验设计提供信息。
Determine relationships between skin gene expression and systemic sclerosis (SSc) clinical disease features, and changes in skin gene expression over time. A total of 339 forearm skin biopsies were obtained from 113 SSc patients and 44 matched healthy controls. 105 SSc patients had a 2nd biopsy, and 76 had a 3rd biopsy. Global gene expression profiling was performed, and differentially expressed genes and cell type-specific signatures in SSc were evaluated for relationships to mRSS and other clinical variables. Changes in skin gene expression over time were analyzed by mixed effects models and principal component analysis. Immunohistochemical staining was performed to validate conclusions. Gene expression dysregulation was greater in SSc patients with affected skin than in those with unaffected skin. Immune cell and fibroblast signatures positively correlated with mRSS. High baseline immune cell and fibroblast signatures predicted higher mRSS over time, but were not independently predictive of longitudinal mRSS after adjustment for baseline mRSS. In early diffuse cutaneous SSc, immune cell and fibroblast signatures declined over time, and overall skin gene expression trended towards normalization. On immunohistochemical staining, most early diffuse cutaneous SSc patients with high baseline T cell and macrophage numbers had declines in these numbers at follow up. Skin thickness in SSc is related to dysregulated immune cell and fibroblast gene expression. Skin gene expression changes over time in early diffuse SSc, with a tendency towards normalization. These observations are relevant for understanding SSc pathogenesis and could inform treatment strategies and clinical trial design.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
27.4
作者：
Gaydosik AM;Tabib T;Domsic R;Khanna D;Lafyatis R;Fuschiotti P
通讯作者：
Fuschiotti P
影响因子：
6.5
作者：
Pendergrass, Sarah A.;Lemaire, Raphael;Francis, Ian P.;Mahoney, J. Matthew;Lafyatis, Robert;Whitfield, Michael L.
通讯作者：
Whitfield, Michael L.
DOI：
10.1016/j.jid.2018.01.006
发表时间：
2018-06
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Hinchcliff M;Toledo DM;Taroni JN;Wood TA;Franks JM;Ball MS;Hoffmann A;Amin SM;Tan AU;Tom K;Nesbeth Y;Lee J;Ma M;Aren K;Carns MA;Pioli PA;Whitfield ML
通讯作者：
Whitfield ML
影响因子：
27.4
作者：
van den Hoogen, Frank;Khanna, Dinesh;Pope, Janet E.
通讯作者：
Pope, Janet E.