Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 399-409
DNA Typing for HLA-A and HLA-B Identifies Disparities Between
Patients and Unrelated Donors Matched by HLA-A and HLA-B Serology and
HLA-DRB1
Vinod K. Prasad,
Nancy A. Kernan,
Glenn Heller,
Richard J. O'Reilly, and
Soo Young Yang
From the Departments of Pediatrics, Bone Marrow Transplantation, and
Biostatistics, Biochemical Immunogenetics Laboratory, Immunology
Program, Memorial Sloan Kettering Cancer Center, New York, NY.
High incidences of graft failure and graft-versus-host disease in
the recipients of bone marrow transplantations (BMT) from unrelated
donors (URD) may reflect the existence of allelic disparities between
the patient and the URD despite apparent HLA identity at HLA-A, HLA-B,
and HLA-DRB1 loci. To identify the extent and pattern of allelic
disparities at HLA-A and HLA-B loci, 128 patients and 484 potential URD
were evaluated by DNA typing. DNA typing for HLA-A, HLA-B, and HLA-DRB1
was performed at Memorial Sloan Kettering Cancer Center. HLA-A and
HLA-B serotyping on URD was provided by the registries. By original
typing (serology for HLA-A and HLA-B; DNA typing for DRB1) 187, 164, and 133 URD were 6/6, 5/6, and 4/6 matches, respectively. Following DNA
typing, however, only 52.9% of the originally 6/6 matched URD remained
6/6, while 38.5%, 7.5%, and 1.1% were found to be 5/6, 4/6, and 3/6
matches. The level of disparity was higher in the originally 5/6 (P
< .01) and 4/6 (P < .01) matched URD. A higher level of
disparity was seen for HLA-B as compared to HLA-A. In addition, a
serotype related variation was also noticed. For example, 24.1% of
HLA-A2 and 60.1% of HLA-B35 seromatched URD were genotypically
disparate, but no disparities were seen for HLA-A1 and HLA-B8. A higher
percentage of HLA-A (67.4%) compared with HLA-B (35.4%) serologic
homozygous URD remained genotypically homozygous (P = .01).
The level of allelic disparity was lower (P < .01 for
6/6; P = .02 for 5/6) if the patient had one of the
15 most common haplotypes (A1B8DR3, A2B7DR15, A3B7DR15, etc) in
comparison to the rest of the group. Outcome studies will answer the
question whether these disparities are associated with a higher rate of
immunological complications seen with URD-BMT.
