ArticleArthritis research & therapy2025
Transcriptome analysis unveils Th1 cell cycle signature as a distinctive feature of mixed connective tissue disease.
Article in Arthritis research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesMixed connective tissue disease (MCTD) is characterized by positivity for anti-U1-RNP antibodies and a combination of symptoms of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and inflammatory myositis (IIM). The aim of this study was to elucidate the similarities and differences in gene expression profiles of peripheral blood immune cells between MCTD and its related diseases, as well as their association with clinical parameters.
methodsTranscriptome analysis was performed in peripheral blood immune cells from 19 MCTD patients, 58 SLE patients, 63 SSc patients, 64 IIM patients, and 79 healthy controls (HC), comprising a total of 283 individuals across 27 immune cell subsets. Differential gene expression and enrichment analyses were conducted to compare MCTD with related diseases and HC. The association between dysregulated pathways in MCTD and clinical parameters was assessed. Gene modular and machine learning analyses were employed to identify related gene signatures in other immune cells.
resultsMCTD exhibited a higher number of differentially expressed genes (DEGs) in Th1 cells compared to other related diseases and HC. Although the DEGs between MCTD and SLE were limited, Th1 cells in MCTD shared common DEGs with each disease, and enrichment analysis revealed upregulation of cell cycle pathways in MCTD Th1 cells. This gene signature showed upregulation in high disease activity and in anti-U1-RNP antibody positive patients in related diseases, and it was associated with severity of Raynaud's phenomenon. Furthermore, the Th1 cell cycle signature correlated with interferon signature in other immune cells.
conclusionsTranscriptome analysis of peripheral blood immune cells revealed that MCTD Th1 cells share many transcriptional features with those in SLE, yet display distinctive cell cycle signature. Particularly, upregulation of cell cycle pathways was associated with characteristic clinical features of MCTD, such as positivity for anti-U1-RNP antibodies and Raynaud's phenomenon. This Th1 cell cycle signature holds promise for shedding light on the underlying pathophysiology of MCTD.
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