Transcriptomic Evaluation of Juvenile Localized Scleroderma Skin With Histologic and Clinical Correlation.

Area of Science:

• Dermatology
• Immunology
• Genomics

Background:

• Juvenile localized scleroderma (LS) is a rare autoimmune skin disease with poorly understood pathogenesis.
• Investigating the skin transcriptome in juvenile LS is crucial for identifying molecular targets and understanding disease mechanisms.

Purpose of the Study:

• To determine the skin transcriptome in juvenile LS using RNA sequencing (RNA-Seq).
• To identify significant molecular targets and correlate gene expression with histopathologic and clinical features.
• To group patients into distinct genetic clusters based on immunophenotype.

Main Methods:

• RNA-Seq was performed on skin biopsy tissue from 28 children with juvenile LS and 10 healthy controls.
• Differentially expressed genes (DEGs) were identified using DESeq2.
• Histologic scoring for inflammation and collagen deposition was correlated with gene expression using Spearman's rank correlation.

Main Results:

• 589 significant DEGs were identified in juvenile LS compared to controls.
• Hierarchical clustering revealed 3 distinct juvenile LS immunophenotype clusters.
• Gene expression of HLA-DPB1, HLA-DQA2, HLA-DRA, and STAT1 correlated with skin inflammation; collagen genes correlated with collagen thickness.

Conclusions:

• Three distinct genetic signatures were identified in juvenile LS, correlating with inflammation and fibrosis.
• One cluster showed up-regulated inflammation pathways, another fibrosis pathways, and a third resembled healthy controls.
• Up-regulation of HLA class II genes in the inflammation cluster is consistent with findings in morphea and systemic sclerosis.