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 Journal Article

Authors: Prasad, V. K.; Kernan, N. A.; Heller, G.; O'Reilly, R. J.; Yang, S. Y.
Article Title: 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
Abstract: 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 sero-matched 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.
Keywords: human tissue; human cell; major clinical study; polymerase chain reaction; genotype; haplotypes; hla matching; tissue donors; dna; nucleotide sequence; hla dr antigen; hla-dr antigens; graft versus host reaction; serodiagnosis; hla a antigen; hla b antigen; bone marrow transplantation; dna determination; hla-a antigens; hla-b antigens; continental population groups; ethnic groups; histocompatibility testing; allelism; humans; human; priority journal; article
Journal Title: Blood
Volume: 93
Issue: 1
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 1999-01-01
Start Page: 399
End Page: 409
Language: English
PUBMED: 9864187
PROVIDER: scopus
DOI: 10.1182/blood.V93.1.399
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Soo Y Yang
    100 Yang
  2. Nancy Kernan
    477 Kernan
  3. Glenn Heller
    369 Heller
  4. Richard O'Reilly
    670 O'Reilly
  5. Vinod K Prasad
    31 Prasad