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

VEXAS综合征变异等位基因频率的监测:数字PCR与下一代测序的比较

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Abstract

BACKGROUND: VEXAS syndrome is an adult-onset, X-linked autoinflammatory disorder resulting from somatic variations in the UBA1 gene. AIM: To evaluate the adequacy of the digital PCR (dPCR) to follow up the variant allele frequency (VAF) on response to the treatment in patients with VEXAS. PATIENT AND METHODS: This study is a 1-year follow-up of a 76-year-old male VEXAS patient treated with azacitidine. The VAF of UBA1 was serially quantified using next-generation sequencing (NGS) and dPCR. RESULTS: There was a high concordance between the two methods. Azacitidine treatment results in a progressive clinical improvement, normalisation of haematologic parameters and a marked reduction in VAF. CONCLUSION: These findings support dPCR as a sensitive and easy-to-manage tool for monitoring therapeutic responses in VEXAS syndrome, providing a method with a quick and cost-effective response. TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.

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