Monitoring Variant Allele Fraction in VEXAS Syndrome: A Comparison of Digital PCR and Next-Generation Sequencing

Area of Science:

• Genetics
• Immunology
• Hematology

Background:

• VEXAS syndrome is an adult-onset autoinflammatory disorder linked to somatic mutations in the UBA1 gene.
• Understanding disease progression and treatment efficacy is crucial for managing VEXAS syndrome.

Purpose of the Study:

• To assess the suitability of digital PCR (dPCR) for monitoring the variant allele frequency (VAF) in VEXAS syndrome patients undergoing treatment.
• To compare dPCR with next-generation sequencing (NGS) for VAF quantification.

Main Methods:

• A 1-year follow-up study of a 76-year-old male VEXAS patient treated with azacitidine.
• Serial quantification of UBA1 gene VAF using both NGS and dPCR.

Main Results:

• High concordance was observed between dPCR and NGS for VAF measurement.
• Azacitidine treatment led to clinical improvement, normalized hematologic parameters, and a significant reduction in UBA1 VAF.

Conclusions:

• Digital PCR (dPCR) is a sensitive, user-friendly, and cost-effective tool for monitoring therapeutic responses in VEXAS syndrome.
• dPCR provides rapid and reliable VAF monitoring for VEXAS syndrome patients.