Background

Human leukocyte antigen (HLA) molecules are located on the short arm of chromosome 6 of humans. It is a polymorphic region of about 3.6M involved in immune response, containing more than 200 genes. Except for identical twins, it is almost impossible to find people with the same HLA. Everyone's HLA varies greatly, making it the most complex genetic system discovered so far. Currently, the IPD-IMGT/HLA database has included 38,008 alleles (version 3.55, 2024-01).

The HLA system consists of three regions

The class I region corresponds to genes such as HLA-A, -B, and -C, and encodes the alpha chain of class I molecules. The beta 2 microglobulin of class I molecules is encoded by genes in non-HLA regions. It also contains non-classical HLA-E, -F, and -G.

The class II region corresponds to genes such as HLA-DR, -DQ, and -DP, and encodes the alpha chain gene (A1) and the beta chain gene (B1). The alpha chain and the beta chain pair to form a functional HLA molecule. Most individuals carry an additional DRB gene (DRB3 or DRB4 or DRB5), which encodes a different beta chain that may pair with the alpha chain.

The class III region, in which genes encode complement system proteins and TNF family genes.

 Naming method 

The World Health Organization HLA Factor Nomenclature Committee established the naming principles for HLA alleles. The current HLA naming system uses a unique number consisting of up to four groups of numbers separated by colons (as shown in the figure).

Detection significance

The typing and detection of HLA class I A, B, and C loci and class II DR and DQ locus alleles play a role in donor-recipient matching for hematopoietic stem cell transplantation, bone marrow transplantation, and other tissue and organ transplants such as liver and kidney. The key role is that the HLA genotype matching degree of both donor and recipient significantly affects the long-term survival rate of the transplant recipient. The higher the matching degree, the higher the long-term survival rate. HLA genotype mainly refers to HLA-A, B, C, DRB1 , DQB1 5 sites. HLA genotyping testing can help establish a hematopoietic stem cell donor bank and conduct HLA population genetic polymorphism analysis. In recent years, the Chinese Bone Marrow Bank is actively advocating high-scoring databases, that is, HLA-A, B, C, DRB1, DQB1, etc. Five genetic loci were tested with 4-digit high-resolution typing in order to fundamentally improve the efficiency of HLA matching.

At the same time, genotyping tests for single loci of HLA-I class B locus such as B27 and B5801 also play an important role in personalized selection of drugs, such as auxiliary diagnosis of ankylosing spondylitis and gout medication guidance. HLA-B*1502 has also been confirmed to be highly associated with Stephen Johnson syndrome in the Han population caused by taking the anti-epileptic drug carbamazepine.

In the approved kits, the methodologies include fluorescent PCR, PCR-melting curve method, PCR-SSP method, PCR-SBT method, etc. With the development of sequencing technology, the second-generation sequencing NGS and the third-generation sequencing TGS or single-molecule sequencing technology are also commonly used in the detection of HLA genotyping. Among them, the PCR-SBT method based on Sanger sequencing is the "gold standard" of HLA typing methods recommended by the World Health Organization.

Based on different testing needs in the market, we have developed HLA standards that can be used for the development of HLA nucleic acid testing kits and quality control of HLA genotyping testing, including ① single HLA locus genotyping ② HLA matching multi-locus genotyping nucleic acid testing standards, covering common alleles in China and HLA-related drug-guided testing sites for customers to choose from.

Product Features

01 HLA typing covers a relatively complete 11 sites A B C DRB1/3/4/5 DPA1 DPB1 DQA1 DQB1, ultra-high resolution typing;

02 Whole genome DNA format, exons and introns are available;

03 PCR-SBT or third-generation sequencing identification, accurate confirmation of typing sequence;

04 Human cell background, better simulation of clinical samples, and reproducibility;

05 Sustainable and stable supply, small batch-to-batch differences;

06 ISO90001 ISO13485 dual system certification, first-class product quality.