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.

Authors

Amanda D Robinson, Clare E Pain, Gabrielle A Morgan, Anwesha Sanyal, Srilakshmi Chaparala, Lauren M Pachman, Kathryn S Torok

Published in

ACR open rheumatology. Volume 8. Issue 3. Pages e90005.

Abstract

To 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.
Peripheral 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 log₂ fold change cutoff of ±1.5 and a false discovery rate of <0.1.
Patients 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.
Patients 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.

PMID:
41757646
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

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