Integrative Transcriptomic Analysis of Peripheral Blood Monocytes in Systemic Sclerosis and Shared Pathogenic...

Area of Science:

• Immunology
• Genomics
• Autoimmune Diseases

Background:

• Systemic sclerosis (SSc) is an autoimmune disease (AD) often overlooked compared to RA, SLE, and pSS.
• Understanding SSc pathogenesis requires analyzing its unique molecular and cellular profiles.

Purpose of the Study:

• To compare transcriptional profiles and immune cell composition in SSc patients against other ADs.
• To identify SSc-specific and shared pathogenic pathways in autoimmune diseases.

Main Methods:

• RNA-sequencing data from 119 untreated patients (SSc, RA, pSS, SLE) and 20 healthy controls.
• Bioinformatics analysis to identify differentially expressed genes (DEGs), biological functions, and immune cell profiles.

Main Results:

• 1,148 DEGs identified in SSc, with upregulated genes linked to megakaryocyte processes and downregulated genes to neutrophil function.
• DEGs like ALDH1A1 and MEGF9 associated with neutropenia; upregulated TFs linked to embryonic hematopoiesis.
• Common pathways in ADs, especially megakaryocyte proliferation; unique SSc genes (MEGF9, MMP8, KRT) suggest roles in neutrophil function, skin integrity, and fibrosis.

Conclusions:

• Dysregulated gene expression (KRT, MMP8) and increased megakaryocytes are identified in SSc, sharing patterns with other ADs.
• Findings provide novel insights into SSc pathogenesis.
• Potential new therapeutic targets for SSc treatment are suggested.