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HLA NULL AND LOW EXPRESSION ALLELES IN THE NATIONAL MARROW DONOR PROGRAM® DONOR/RECIPIENT PAIR PROJECT.
Hugo A. Araujo , Stephen Spellman , Rebecca Cullen , Arend Mulder , Laurie Burdett , Kanthi Kariyawasam , Lee Ann Baxter-Lowe , Thomas Williams , William Hildebrand , Jennifer Ng , Carolyn K. Hurley , Robert Hartzman and Marcelo A. Fernandez-Vina . Kensington MD, Naval Medical Research Center/Georgetown University, CW Bill Young DoD Marrow Donor Program ; Minneapolis MN, National Marrow Donor Program ; Leiden Netherlands, Leiden University Medical Center ; San Francisco CA, UCSF ; Albuquerque NM, University of New Mexico ; Oklahoma City OK, University of Oklahoma and Washington DC, Georgetown University, Department of Oncology, Lombardi Cancer Center .

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HLA low and null alleles have important implications in the selection of unrelated bone marrow donors when DNA-based testing is used as the only method to assign phenotypes. Diverse genetic events alter the expression levels of HLA alleles and they are not routinely assessed. We have examined the donors of 3,417 unrelated bone marrow transplant pairs from a NMDP study. HLA has been typed prospectively by serology and retrospectively by DNA methods. Selection criteria included individuals having a single serologic HLA specificity and two DNA defined alleles belonging to distinct serotypes. We identified 10 donors with discordant serology/DNA results involving HLA-A alleles. To rule out serologic mistyping, B-cell lines were tested with a set of HLA mAb (labeled with Alexa 488) by flow cytometry. Serological misses were observed in 8 donors (A*7401/2 in 3 subjects; A*3301 in 3 subjects; A*8001and A*3201 in one subject each). HLA sequence based typing identified A*2411N and A*24020102L in 2 donors. Overall, we found serologic misses in approximately 0.23% of the donors. Similarly, serological misses in recipients were associated with two A*7401, one A*0101 and one A*1101 alleles. A*6811N and A*2409N were identified in 2 recipients. All null/low HLA-A alleles found in this study (<0.06% of donors) have been previously described