idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
idw - Informationsdienst
Wissenschaft
World Laboratory Day takes place on April 23. The DKMS Life Science Lab (LSL), based in Dresden, Germany, is the world's leading HLA typing laboratory. Around 1.2 million samples of potential stem cell donors are analyzed here every year. In addition, the DKMS laboratory makes an important contribution to medical research and optimizes the search for suitable stem cell donors. The typing specialists at LSL have already discovered almost 6,000 previously unknown HLA gene variants (alleles) and made them available to the international HLA allele database. This benefits physicians and their patients worldwide.
For many blood cancer patients, a stem cell transplant is the only hope. Those who cannot find a donor in their own family are dependent on an unrelated donor - this affects around 70,000 people worldwide every year. To give as many of them as possible a second chance at life, more than one million people register with DKMS each year.
Their buccal swab samples, up to 7,000 per day, are analyzed in the DKMS Life Science Lab in Dresden. This process is called HLA typing and is essential to identify suitable stem cell donors. HLA characteristics are protein structures on the surfaces of all cells and occur in different combinations in every individual, much like fingerprints. They form the "signature" of the cells, with the help of which the immune system distinguishes between endogenous and exogenous structures. The better the HLA characteristics of donor and recipient match, the lower the risk of possible rejection reactions. The matching of HLA characteristics is therefore one of the most important success factors for a stem cell transplant.
Therefore, DKMS and the DKMS Life Science Lab place particular emphasis on the high typing quality of all registered donors. Currently, the typing profile includes twelve HLA gene loci with 24 high-resolution tissue characteristics, as well as other relevant criteria for donor selection, such as CMV status, blood group (ABO and RhD) and KIR receptor group. 170 laboratory staff process more than one million cheek swab samples from newly registered stem cell donors per year. This is possible with the help of Next Generation Sequencing (NGS), a technology that the DKMS Life Science Lab was the first laboratory ever to use for high-throughput typing in 2013.
New HLA alleles found in more than 34,500 cases
The specialists at the DKMS Life Science Lab keep discovering "new", previously unseen alleles due to the large number of typing they analyze every day. An allele is a variant of a gene that distinguishes different individuals. A special department of the laboratory is dedicated to the in-depth analysis of these new alleles and thus makes a decisive contribution to the further development of the international HLA reference database for allele sequences (IPD-IMGT/HLA database). This database provides public access to the sequencing information of all known gene variants or alleles and serves as a reference for all laboratories, clinics and research institutions worldwide that perform HLA analyses.
Since 2010, the experts of the DKMS Life Science Lab have found new HLA alleles in more than 34,500 cases (as of April 2021). Since then, they have submitted 5,848 new alleles to the international database. Of these, 3,407 have received their own name to date and have been officially added to the reference database. From this point on, the search for a matching donor with such an allele has only become possible.
Two sequencing methods for maximum safety
If the typing process reveals that a gene variant is not yet known in the international reference database, it is completely sequenced again in the DKMS Life Science Lab. The experts use two different sequencing methods (NGS and PacBio) to completely exclude sequencing errors. The release of the IPD-IMGT/HLA database contained a total of 27,059 HLA alleles at the end of 2020. Of these, only 44% (11,845 alleles) were fully characterized. Nearly one-third (29%) of the fully characterized alleles were disclosed by the DKMS Life Science Lab. And thanks to the dedicated work of the Dresden typing specialists, the number is increasing daily: the DKMS Life Science Lab is pursuing further projects to expand the international reference database. The focus is on genes that are particularly challenging due to their length or structure and are therefore only fragmentarily represented in the database. Currently, the laboratory is working on the characterization of alleles of the genes HLA-DQB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DMA, HLA-DMB, HLA-DOA, MICA and MICB. In addition to previously unknown alleles, alleles that have only been partially described in the database are also characterized. In this way, the DKMS laboratory makes a significant contribution to the permanent improvement of the reference database and thus supports the important work of all clinics, research institutions and laboratories that access it.
https://professional.dkms.org/about/life-science-lab further information about DKMS Life Science Lab
https://professional.dkms.org/research-publications/publications/Behrens2020 publications
http://www.ebi.ac.uk/ipd/imgt/hla/ IPD-IMGT/HLA Database
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