HLA-C disparity between patients and unrelated donors matched for HLA-A, -B, and -DRBI alleles: Impact of serological vs. DNA typing for HLA-A and -B loci Journal Article

Authors: Prasad, V. K.; Kernan, N. A.; Heller, G.; O'Reilly, R. J.; Yang, S. Y.
Article Title: HLA-C disparity between patients and unrelated donors matched for HLA-A, -B, and -DRBI alleles: Impact of serological vs. DNA typing for HLA-A and -B loci
Abstract: High incidences of graft failure, graft-vs.-host disease (GVHD), and serious infections following unrelated donor (URD) marrow transplantation, despite apparent human leukocyte antigen (HLA) identity, may reflect the presence of molecular disparities, including those for HLA-C alleles between the patient and the URD. The level of these disparities could be significant, because as many as 42 alleles are currently known for HLA-C locus. We studied 84 patients and 251 potential URDs to evaluate 1) the extent of HLA-C disparity between the patient and the URD identified by serology for HLA-A and -B and by DNA typing for -DRB1 and 2) the level of HLA-C disparity between patients and URDs matched by high-resolution DNA typing for HLA-A, -B, and -DRB1. The DNA typing was performed at the Memorial Sloan Kettering Cancer Center, and the serotyping was provided by the registries. Of 251 URDs matched by HLA-A and -B serology and -DRB1 (sA_sB_dnaDRB1); 94, 75, and 82 were 6/6, 5/6, and 4/6 matches, respectively. Of 94 sA_sB_dnaDRB1 6/6 URDs, 51 (54.3%) were matched for both HLA-C alleles. In contrast, 31 (41.3%) 5/6 (p = 0.12) and 15 (18.3%) 4/6 (p < 0.01) sA_sB_dnaDRB1 URDs were matched for both HLA-C alleles. Following DNA typing for HLA-A and -B, 52 (55.3%) of 94 6/6, 30 (40%) of 75 5/6, and 25 (30.5%) of 82 4/6 sA_sB_dnaDRB1 URDs remained 6/6, 5/6, and 4/6 matches at the DNA level (dnaA_B_DRB1). HLA-C disparities continued to exist in the dnaA_B_DRB1 URD group. Of 54 dnaA_B_DRB1 6/6 URDs, 41 (75.9%) were matched for both HLA-C alleles. Only 45.3% of the 5/6 (p = 0.01) and 22.2% of the 4/6 (p < 0.01) dnaA_B_DRB1 URDs were matched for both HLA-C alleles. In the 6/6 category, the frequency of HLA-C matching improved (75.9 vs. 54.3%; p = 0.01) following DNA matching for HLA-A and -B. In comparison to mismatching for HLA-B locus, mismatching for either HLA-DRB1 or -A resulted in a lower odds ratio for HLA-C disparity. The presence of a common haplotype in the sA_sB_dnaDRB1 (p = 0.06) URD category improved the level of HLA-C matching. We identified alleles that are associated with high (B*1501, B*4402, B*5101, DRB1*0101, A*0201, A*1101, A*2301, and A*3201) or low (B*0702, B*0801, B*1302, B*3502, DRB1*0301, DRB1*1104, A*0101, A*3001, and A*6801) probability of HLA-C disparity. Overall, sA_sB_dnaDRB1 as well as dnaA_B_DRB1 matched URDs for non-Caucasian patients were more likely to have HLA-C disparity in comparison to the matched URDs of Caucasian patients. However, a high incidence of HLA-C disparities was identified even in the URDs for Caucasian patients. Whether the disparities demonstrated by this study contribute to the higher immunological complications noted following URD bone marrow transplantation is unclear. Outcome analysis and studies aimed at understanding the functional role of HLA-C may provide an answer.
Keywords: genetics; methodology; immunology; dna; hla dr antigen; hla-dr antigens; hla a antigen; hla b antigen; bone marrow transplantation; hla-a antigens; hla-b antigens; transplantation immunology; histocompatibility; unrelated donor; histocompatibility testing; histocompatibility test; humans; human; article; dna typing; molecular disparity; hla-drb1 antigen
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 5
Issue: 2
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 1999-03-01
Start Page: 77
End Page: 85
Language: English
PUBMED: 10371359
PROVIDER: scopus
DOI: 10.1053/bbmt.1999.v5.pm10371359
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
    370 Heller
  4. Richard O'Reilly
    670 O'Reilly
  5. Vinod K Prasad
    31 Prasad