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

Objective 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. Methods 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 log 2 fold change cutoff of ±1.5 and a false discovery rate of