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The major histocompatibility complex (MHC), known as the human leukocyte antigen (HLA), is the most polymorphic region in humans. The extensive polymorphism of the HLA region is believed to have been driven by the evolutionary pressure to detect and mount an immune response to infectious pathogens.
Molecular typing for HLA involves identifying specific HLA genes and their variants at the DNA level. This precise method uses techniques like PCR and sequencing to determine exact nucleotide sequences, vital for transplant compatibility, disease association studies, and personalized medicine.
The complexity and number of antigens identified can be accessed at: http://hla.alleles.org/alleles/index.html
Importance of typing resolution
HLA typing is crucial for determining compatibility in organ and bone marrow transplantation and disease association studies. The resolution of HLA typing refers to the level of detail in identifying HLA alleles. Higher resolution typing provides more precise and detailed identification of alleles, which is important for:
- Transplant compatibility: Ensuring a closer match between donor and recipient HLA alleles reduces the risk of transplant rejection and improves graft survival.
- Disease association studies: High-resolution typing allows for more accurate associations between specific HLA alleles and diseases.
The choice of technique is influenced by the type of sample, the required turnaround time for results, and the desired resolution. Most laboratories employ a combination of techniques and tests to deliver comprehensive HLA typing services.
The level of resolution of the technology employed will depend on the type of transplant and the urgency of obtaining the result. For instance, HLA testing to determine stem cell compatibility typically involves multiple rounds of testing and comparison and does not face the same time constraints as a deceased donor kidney transplant, where timely results are critical to the success of the transplant and the viability of the organ.
Polymerase chain reaction (PCR) is a widely used molecular biology technique designed to amplify specific segments of DNA, producing millions to billions of copies from a small initial sample. This process enables detailed analysis and manipulation of DNA sequences.
Traditional techniques include serological typing, PCR using sequence-specific primers (SSP) and sequence-based typing (SBT) and these still play an important role in HLA typing globally, even as new technologies emerge.
The introduction of Luminex technology which utilizes PCR-SSOP (sequence-specific oligonucleotide probes) for HLA typing allows multiplex testing typing and labs can batch test large volumes of samples.
The need and demand for high-resolution typing have driven advancements in sequencing technologies. The community has witnessed progress from Sanger sequencing-based typing (SBT) to next generation sequencing (NGS), enabling laboratories to achieve the highest resolution of HLA testing. These advancements enhance matching accuracy and assist in identifying the best donor!
| Low resolution - Serological/Antigen level | Medium resolution - Intermediate | High resolution - Allele level | |
| Description | Identifies broad HLA groups or serotypes | Provides more detailed allele group information but not the specific sequence | Identifies the specific nucleotide sequence of HLA alleles |
| Testing methodology by examples |
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The information presented on this website is intended solely for educational and general informational purposes. It is not intended to provide medical advice, constitute clinical guidance, or serve as a substitute for professional judgment in patient care.