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Scoring for HLA matching? A clinical test of HistoCheck

Bone Marrow Transplantation volume 34, pages 367–368 (2004)Cite this article

The HistoCheck1 software is offered as a tool ‘that is capable of assessing the allogenicity (matching score) between any pair of clinically relevant HLA class I… alleles’. This is a brave attempt to aid Transplant Physicians in making the often difficult choice between two or more mismatched (unrelated) donors, when no completely matched donor is available. This internet-based software provides a score that takes into account both the functional and the structural difference between two HLA alleles at one locus. The predictive value of HistoCheck is based on the presumption that transplant success is improved by selecting a donor with an HLA type most similar to the patient.

Although there are limited data published to suggest transplants with allele mismatches fare better than antigenic mismatches,2 our knowledge of the biology of HLA suggests that limited polymorphic differences are unlikely to be significantly less immunogenic than numerous differences. This is because limited polymorphisms are not functionally null. Polymorphism is focused at residues that line the peptide-binding groove and at the surface recognised by T-cell receptors. Thus, HLA variants confer a phenotyping change presumed to provide a selective advantage in the fight against invading pathogens.3 We know small differences between MHC molecules influence T-cell recognition. Indeed, prior to DNA sequencing, serologically defined groups of related HLA variants were subdivided on the basis of their differential reactivity with alloreactive T cells.4, 5 The report describing bone marrow transplant rejection induced by a single amino-acid variant demonstrates that small differences are sufficient for development of in vivo alloreactivity.6 It has even been suggested that limited differences may induce stronger alloresponses than numerous differences7, 8 because the foreign MHC molecule closely resembles self-MHC and is therefore more likely to crossreact with self-educated T cells. The impact of qualitative differences is contentious.

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  1. Anthony Nolan Trust, Royal Free Hospital, London

    B E Shaw, L D Barber, J A Madrigal, S Cleaver & S G E Marsh

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  1. B E Shaw
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  2. L D Barber
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  3. J A Madrigal
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  4. S Cleaver
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  5. S G E Marsh
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Shaw, B., Barber, L., Madrigal, J. et al. Scoring for HLA matching? A clinical test of HistoCheck. Bone Marrow Transplant 34, 367–368 (2004). https://doi.org/10.1038/sj.bmt.1704586

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