Table. 1.

Overview of different HLA typing techniques

Typing method Basic mechanism Advantages Disadvantages
Serologic method Detection of HLA molecules using antisera • Rapid screening
• Suitable for deceased donor typing
• Low resolution
• Limited availability of serological reagents
• Typing limited to known alleles
SSO Hybridization with short oligonucleotide DNA probes Multiple sample typing • Low to intermediate resolution
• Typing limited to known alleles
• Certain amount of ambiguities
SSP Amplification of HLA alleles with sequence-specific primers • Low cost
• Applicable for deceased donor
• Different resolutions can be obtained depending on the primers
• Unsuitable for large numbers of samples
• Low to intermediate resolution
• Typing limited to known alleles
• Certain amount of ambiguities
SBT Direct DNA sequencing • High resolution
• Able to sequence novel alleles
• Requires longer time
• High cost
• Unable to set phase between polymorphisms
• Not suitable for deceased donor typing
NGS Sequencing of small fragments of DNA in parallel • High resolution
• High throughput
• Able to sequence novel alleles
• Low ambiguity
• Whole-gene coverage
• Expensive sequencer
• Requires suitable software for analysis
• Not suitable for deceased donor typing
TGS • Individual DNA molecule sequencing in real time (PacBio SMRT sequencing)
• Single DNA molecule sequencing through a nanopore (Oxford Nanopore sequencing)
• High resolution
• Able to sequence novel alleles
• Low ambiguity and phasing
• Whole-gene coverage
• Applicable for deceased donor typing (Oxford Nanopore sequencing)
• Expensive equipment
• Relatively high error rate
• Require suitable bioinformatics tools

HLA, human leukocyte antigen; SSO, sequence-specific oligonucleotide; SSP, sequence-specific primers; SBT, sequence-based typing; NGS, next-generation sequencing; TGS, third-generation sequencing, SMRT, Single-Molecule Sequencing in Real Time.

Clin Transplant Res 2024;38:294~308 https://doi.org/10.4285/ctr.24.0055