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HLA cell-surface proteins allow the body to identify itself to avoid autoimmune reactions. Every person has a unique HLA signature. HLA proteins also identify foreign invaders in the body. "Their primary purpose is to distinguish, self versus non-self," explains Kamoun. "That's why we need to immunosuppress recipients following transplantation."
The researchers looked at genetic variations in recipient and donor HLA proteins from blood samples (blood cells express HLA proteins) taken from 697 kidney transplant recipients and their deceased donors to obtain paired samples.
HLAs come in a variety of forms, differing by the sequence of their building blocks, or amino acids, from individual to individual. "Donor-recipient matching is based on genetic variations in HLA proteins," says Kamoun. "By examining the HLA amino acid sequences of donor-recipient pairs, we asked: Are these genetic differences significantly associated with the recipient's experience of DGF?"
Out of 66 amino-acid variations in HLA-A proteins, they found 15 were more strongly associated with DGF. They then focused on those, and taking other non-immunological factors into account, narrowed the important differences down to three amino acids that were highly associated with DGF. These are amino acids that play an important role in how pieces of foreign proteins are presented to immune cells. HLA proteins display these foreign molecules to specific recipient immune cells, called T lymphocytes.
Next steps for the project are to use a larger sample size from the UNOS database. Instead of looking at several hundred, they plan to look at thousands of donor-recipient pairs to validate their findings. "We also expect to see that these critical amino acids for DGF will vary with race," predicts Kamoun. Future studies will also include the evaluation of other clinical outcomes such as acute rejection and graft loss.
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| Contact: Karen Kreeger karen.kreeger@uphs.upenn.edu 215-349-5658 University of Pennsylvania School of Medicine Source:Eurekalert |
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 Understanding donor-recipient genetics could decrease early kidney transplant complications |
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