ArticleACR open rheumatology2026
Distinct by Design: Unraveling the Unique Clinical and Transcriptomic Identity of Juvenile Scleromyositis Overlap Compared to Juvenile Systemic Sclerosis and Juvenile Dermatomyositis: Implications for Care and Pathogenesis.
Article in ACR open rheumatology, 2026. 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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7 authors.
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Abstract
objectiveTo characterize clinical and transcriptomic differences in juvenile scleromyositis overlap (jOverlap) compared to juvenile systemic sclerosis (jSSc) and juvenile dermatomyositis (JDM), focusing on autoantibody profiles, organ involvement, treatment, and peripheral blood gene expression.
methodsPeripheral blood bulk RNA sequencing was performed on children with jSSc (n = 25), JDM (n = 25), and jOverlap (n = 26), and healthy controls (HCs; n = 21) from two tertiary referral centers. Disease category was assigned by treating physicians. Clinical data and autoantibody profiles were collected. RNA was sequenced using the Illumina NextSeq 500 platform. Differentially expressed genes (DEGs) were identified using Partek Flow and DESeq2, applying a log
resultsPatients with jOverlap, predominantly White girls, had distinct autoantibody patterns enriched for PM-Scl, U1-RNP, and U3-RNP. Compared to HCs, patients with jSSc, JDM, and jOverlap demonstrated a unique gene expression profile, with up-regulation of type-1 interferon-related genes, specifically SIGLEC1 and IFI27. Compared to patients with JDM, patients with jOverlap showed higher expression of RAB13 (linked to sclerosing neurodegenerative disease), MMEL1 (inflammatory arthritis), and MMP19 (pulmonary fibrosis). t-distributed stochastic neighbor embedding clustering revealed that although HC, jSSc, and JDM samples each formed distinct clusters, jOverlap samples were distributed across all clusters, highlighting their heterogeneity.
conclusionPatients with jOverlap exhibited a distinct immunophenotype and clinical profile compared to patients with jSSc and JDM. Their broad transcriptional heterogeneity suggests disease category alone does not explain gene expression patterns. Further analysis correlating DEGs with autoantibodies, age, and clinical features is warranted to better define this overlapping disease entity.
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