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Background: The current economic and social crisis in Latin America has caused migration to the USA, bringing with it Public Health challenges due to the importation of various infectious diseases. Migrants, particularly those with chronic conditions, such as HIV infection and other sexually transmitted infections (STI), are at greater risk due to pharmacological interruption and access to medical care, so the timely detection of diseases acquired during their migration, such as malaria, is crucial to avoid health complications.

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Harnessing global HLA data for enhanced patient matching in iPSC haplobanks.

Cytotherapy

November 2024

Scottish National Blood Transfusion Service, Edinburgh, UK; Global Alliance for iPSC Therapies, Jack Copland Centre, Heriot-Watt Research Park, Edinburgh, UK.

Background: Several countries have either developed or are developing national induced pluripotent stem cell (iPSC) banks of cell lines derived from donors with HLA homozygous genotypes (two identical haplotypes) prevalent in their local populations to provide immune matched tissues and cells to support regenerative medicine therapies. This 'haplobank' approach relies on knowledge of the HLA genotypes of the population to identify the most beneficial haplotypes for patient coverage, and ultimately identify donors or cord blood units carrying two copies of the target haplotype.

Aims: A potentially more efficient alternative to a national bank approach is to assess the haplotypes required to provide global patient coverage and to produce a single, global haplobank.

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The degree of immunological compatibility between donors and recipients greatly impacts allograft survival. In the United States kidney allocation system, HLA antigen-level matching has been shown to cause ethnic disparities and thus, has been de-emphasised. However, priority points are still awarded for antigen-level zero-ABDR matching, zero-DR matching and one-DR matching.

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HLA typing and matching have been crucial in kidney transplantation, but methods for assessing tissue histocompatibility have advanced significantly. While serological-level HLA typing remains common, it captures only a small fraction of true HLA variation, and molecular matching is already replacing traditional HLA matching. Recent studies have expanded our understanding of genetic tissue compatibility beyond HLA loci.

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Context: Mucopolysaccharidosis (MPS) requires urgent treatment to prevent neurological damage. While gene therapy holds promise for effectively treating these diseases with minimal toxicity, access remains limited for most patients. Consequently, advancing allogeneic hematopoietic stem cell transplantation (HSCT) for young children is crucial.

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