Ask A Scientist: How Many Donors Does It Take to Cover All HLA Types?

How many donors would it take to cover all of the HLA types? 

It’s a question I’ve been asked several times over the years but have struggled to answer with clarity. 

HLA genes are the most diverse in the human genome. With multiple genes having hundreds if not thousands of alleles, an accurate answer to this question would take much more sophisticated mathematics and statistics than an immunologist like myself could muster. 

Thankfully, a recent publication from the FDA’s Center for Biologics Evaluation and Research (CBER) has proposed a tool to answer this exact question. 

“If, and this is often the case, immune responses to the therapeutic-protein are HLA restricted, ensuring that a representative distribution of HLA variants is included in the clinical and non-clinical studies is very difficult.”

-McGill, et. al. Frontiers in Immunology. 2019.

 

The SampPick Algorithm

The tool is called SampPick, software that can select donors to match a population of interest based upon HLA types. The paper used HLA-DRB1 as a test case, but suggests that the software can be used to include additional genes or loci. While the actual algorithm and calculations shown are not within my area of expertise, the discussion around the problem of HLA matching and the differences among populations was very informative. 

 

Why HLA Typing is Important

The distribution of HLA alleles is different depending on geography. Alleles that are prevalent in Northern European populations are not as prevalent in China or Japan, for example. While researchers should select donors with HLA types that match the population being studied, many rely on random donor selection, which as the authors point out, will not provide the desired HLA matching. 

The authors’ iterative computation — which aims to eliminate the selection bias inherent in donor sourcing from community blood banks and research subjects alike — helps to optimize cohort selection to closely match the allele frequency distribution of the population of interest, as well as determines the number of donors required to provide the desired matching. 

“The immense diversity of the HLA repertoire raises many technical questions in the design of a study. How many HLA variants should be studied? How does one generate a suitable cohort that considers the relative frequencies of HLA variants in different human populations? For an ex vivo assay how many samples should be used? What HLA types should the donors of the cells have? The answers to many of these questions will depend on the drug, the disease and the specific question(s) the study is being designed to answer.”

-McGill, et. al. Frontiers in Immunology. 2019.

 

Doing Our Part

The better we as immunologists can get at HLA typing and donor selection, the more accurate and applicable our research findings can be. 

For our part, we promise to deliver detailed HLA typing and other donor details to help inform your donor selection. View any of our immune cell products to see the donor’s blood type, age, gender, ethnicity, health, HLA type, and more — just like this example from our HLA-A*0201 Restricted Anti CMV T Cells:

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