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Choice of bone marrow donors could improve

BMJ 1998; 316 doi: http://dx.doi.org/10.1136/bmj.316.7131.571l (Published 21 February 1998) Cite this as: BMJ 1998;316:571
  1. Abi Berger
  1. London

    The identification of the DNA structure of a cell surface antigen may help to improve the selection of suitable donors of bone marrow transplants.

    Despite careful matching of donors and recipients, up to 30% of people who undergo sibling bone marrow transplants suffer severe graft versus host disease. The disease occurs when donor cytotoxic T lymphocytes attack host organs such as the skin, gut, and liver, and it can be fatal. Immunologists in the Netherlands and the United States have identified the DNA structure of a cell surface antigen, which is the only one so far recognised to correlate with the development of severe graft versus host disease (Science 1998;279:1054-7).

    Some patients develop graft versus host disease despite having identical human leucocyte antigen (HLA) with their donor. For these people, the attack on their own organs is clearly not due to a mismatch of the major histocompatibility complex but a disparity between other “minor” histocompatibility antigens. The antigens are also found on cell surfaces. For some time it has been known that these minor antigens are located on the Y chromosome and that severe disease correlates strongly with a mismatch in one specific minor antigen, HA-1.

    Joke den Haan and his colleagues have found that HA-1 comes from a single gene, which appears in two forms: people seem to be either HA-1 positive or HA-1 negative. The difference between these two forms is just one amino acid, or two nucleotides at the DNA level. The only case where severe graft versus host disease will occur is when the donor is HA-1 negative and the recipient is HA-1 positive.

    Knowing the DNA structure of the HA-1 gene will greatly improve the matching of potential donors with patients who need transplants. Not only can HA-1 mismatches be identified, but if there is only an HLA matched donor available it will be possible to predict who will most benefit from prophylaxis against graft versus host disease. Testing for the presence of the HA-1 antigen will add just seconds to the DNA typing already carried out when potential donors are matched to recipients. “This work is critically important,” said Dr Mike Potter, senior lecturer in haematology at the Royal Free Hospital in London. “It could be the key to understanding T cell recognition in relation to transplantation.”

    There may be a slight down side to this discovery. There is a well known graft versus leukaemia effect, where graft cells actually kill residual leukaemia cells in the patient. If the HA-1 antigen is always matched in the donor and recipient, and graft versus host disease does not occur, the graft versus leukaemia effect will also be lost. “What we don't know is if we always match for HA -1 whether we will end up with more recurrent leukaemia,” admitted Dr Els Goulmy, who heads the Dutch team. For some diseases, such as chronic myeloid leukaemia, where the graft versus leukaemia effect is integral to curing the disease, it may be more important to allow some graft versus host disease to develop to reap the benefit of the graft versus leukaemia effect.

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