Next Generation Sequencing of Human Platelet Antigens for Routine Clinical Investigations and Donor Screening

Area of Science:

• Immunogenetics
• Molecular Diagnostics

Background:

• Human platelet antigen (HPA) genotyping is crucial for immune-mediated thrombocytopenia and HPA-matched platelet transfusions.
• Current gold-standard HPA genotyping relies on single nucleotide variant (SNV) based methods.

Purpose of the Study:

• To evaluate if next-generation sequencing (NGS) can replace SNV-based genotyping for HPA systems.
• To assess the concordance between NGS and SNV-based methods for HPA genotyping.

Main Methods:

• A systematic review and meta-analysis were conducted following PRISMA guidelines.
• Six studies comparing NGS and SNV-based HPA genotyping (HPA-1 to -5, -15) were included.
• Data on study quality, characteristics, and results were extracted.

Main Results:

• A pooled proportion agreement of 0.998 (95% CI [0.995, 0.999]) was observed for overall concordance between NGS and SNV-based methods.
• Discrepancies favored NGS, attributed to allele dropout in real-time PCR.
• NGS platforms face limitations including high costs, data handling, variant calling accuracy, and staff training.

Conclusions:

• NGS demonstrates high concordance with established HPA genotyping techniques.
• Significant practical and financial challenges currently limit NGS's viability as a standalone HPA typing method.