A blueprint for electronic utilization of ambiguous molecular HLA typing data in organ allocation systems and virtual crossmatch
Autor: | Geoffrey Smith, Navchetan Kaur, Anat R. Tambur, Malek Kamoun, Robert A. Bray, Marcelo J. Pando, Loren Gragert, David F. Pinelli, Evan P. Kransdorf, Cathi Murphey |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Manual interpretation medicine.medical_specialty Computer science Immunology Computational biology Human leukocyte antigen Organ transplantation 03 medical and health sciences Molecular typing 0302 clinical medicine HLA Antigens medicine Immunology and Allergy Humans Typing Hla genotype Deceased donor Internet Histocompatibility Testing Patient Selection General Medicine Organ Transplantation 030104 developmental biology Imputation (genetics) Software 030215 immunology |
Zdroj: | Human immunology. 81(2-3) |
ISSN: | 1879-1166 |
Popis: | Virtual crossmatch (VXM) compares a transplant candidate's unacceptable antigens to the HLA typing of the donor before an organ offer is accepted and, in selected cases, supplant a prospective physical crossmatch. However, deceased donor typing can be ambiguous, leading to uncertainty in compatibility prediction. We have developed a prototype web application that utilizes ambiguous HLA molecular typing data to predict which unacceptable antigens are present in the donor HLA genotype as donor-specific antibodies (DSA). The application compares a candidate's listed unacceptable antigens to computed probabilities of all possible two-field donor HLA alleles and UNOS antigens. The VIrtual CrossmaTch for mOleculaR HLA typing (VICTOR) tool can be accessed at http://www.transplanttoolbox.org/victor. We reanalyzed historical VXM cases where a transplant center's manual interpretation of molecular typing results influenced offer evaluation. We found that interpretation of ambiguous donor molecular typing data using imputation could one day influence VXM decisions if the DSA predictions were rigorously validated. Standardized interpretation of molecular typing data, if applied to the match run, could also change which offers are made. HLA typing ambiguity has been an underappreciated source of immunological risk in organ transplantation. The VICTOR tool can serve as a testbed for development of allocation policies with the aim of decreasing offers refused due to HLA incompatibility. |
Databáze: | OpenAIRE |
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