Chromosomal Instability and Telomere Attrition in Systemic Sclerosis: A Historical Perspective

Area of Science:

• Genomics
• Autoimmune Diseases
• Cellular Biology

Background:

• Systemic sclerosis (SSc) is a rare autoimmune disease causing fibrosis.
• The exact pathogenesis of SSc remains unclear.
• Chromosomal instability and telomere attrition are key areas of SSc research.

Purpose of the Study:

• To review the role of genomic anomalies in SSc pathogenesis.
• To synthesize historical and current research on SSc.
• To explore genotoxic factors, chromosomal aberrations, and telomere biology in SSc.

Main Methods:

• Historical narrative review.
• Synthesis of foundational and recent research articles.
• Investigation of genotoxic factors, chromosomal aberrations, and telomere biology in SSc.

Main Results:

• Chromosomal instability (micronuclei, translocations, breaks) is evident in SSc, driven by clastogenic factors and oxidative stress.
• SSc autoantibodies (anti-centromere, anti-topoisomerase I) correlate with genomic anomalies and may impair DNA repair.
• Significant telomere attrition occurs in SSc, linked to reduced telomerase activity and autoantibodies against telomere-associated proteins.

Conclusions:

• Inflammation, telomere attrition, and chromosomal instability form a self-perpetuating cycle in SSc pathogenesis.
• Inflammatory stimuli may cause oxidative stress, leading to telomere damage and attrition.
• Critically short telomeres can trigger faulty DNA repair, causing genomic instability and further inflammation, perpetuating fibrosis.