Systemic Sclerosis in Kazakh Patients: A Preliminary Case-Control Immunogenetic Profiling Study

Area of Science:

• Immunogenetics
• Rheumatology
• Human Genetics

Background:

• Systemic sclerosis (SSc) is a complex autoimmune disease marked by immune dysregulation, vascular damage, and fibrosis.
• Understanding the genetic factors and autoantibody profiles is crucial for diagnosing and treating SSc.
• Kazakhstan's unique population presents an opportunity to study potential regional variations in SSc pathogenesis.

Purpose of the Study:

• To investigate the genetic architecture of SSc in a Kazakh cohort.
• To analyze the autoantibody profile in Kazakh patients with SSc.
• To identify potential genetic variants associated with SSc in this population.

Main Methods:

• Analyzed autoantibody profiles (Scl-70, CENP-B, etc.) and IL-6 levels in 26 Kazakh SSc patients and 18 healthy controls.
• Utilized a custom AmpliSeq panel targeting 120 immune/fibrosis genes for genetic analysis via Ion Proton sequencing.
• Employed Fisher's exact test and Chi-square tests for statistical analysis of categorical variables.

Main Results:

• Detected a range of autoantibodies (Scl-70, CENP-B, SS-A/Ro60, etc.) in SSc patients, absent in controls.
• Identified likely pathogenic variants in immune regulatory genes (SAMD9L, REL, IL6ST, etc.) and variants of uncertain significance.
• Discovered novel variants in LY96, PTPN22, IRAK1, and SAMD9L not previously associated with SSc.

Conclusions:

• The study presents the first immunogenetic analysis of SSc in Kazakhstan, revealing a polygenic architecture.
• Findings suggest partial overlap with international SSc cohorts but also highlight region-specific genetic variations.
• Further research with larger sample sizes and functional validation is needed to confirm pathogenic mechanisms and clinical relevance.