A High Degree of HLA Disparity Arises From Limited Allelic Diversity: Analysis of 1775 Unrelated Bone Marrow Transplant Donor-Recipient Pairs

Carolyn Katovich Hurley; Marcelo Fernandez-Vina; William H. Hildebrand; Harriet J. Noreen; Elizabeth Trachtenberg; Thomas M. Williams; Lee Ann Baxter-Lowe; Ann B. Begovich; Effie Petersdorf; Annamalai Selvakumar; Peter Stastny; Janet Hegland; Robert J. Hartzman; Michael Carston; Sharavi Gandham; Craig Kollman; Gene Nelson; Stephen Spellman; Michelle Setterholm

doi:10.1016/j.humimm.2006.09.004

A High Degree of HLA Disparity Arises From Limited Allelic Diversity: Analysis of 1775 Unrelated Bone Marrow Transplant Donor-Recipient Pairs

Carolyn Katovich Hurley, Marcelo Fernandez-Vina, William H. Hildebrand, Harriet J. Noreen, Elizabeth Trachtenberg, Thomas M. Williams, Lee Ann Baxter-Lowe, Ann B. Begovich, Effie Petersdorf, Annamalai Selvakumar, Peter Stastny, Janet Hegland, Robert J. Hartzman, Michael Carston, Sharavi Gandham, Craig Kollman, Gene Nelson, Stephen Spellman, Michelle Setterholm

Pediatrics - Blood/Marrow Transplant

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

The allelic diversity and associated human leukocyte antigen (HLA) disparity of 1775 bone marrow recipients and their unrelated donors, matched for six of six (1361/1775,77%), five of six (397/1775, 22%), or four of six (17/1775, 1%) HLA-A, -B, -DR antigens, were retrospectively evaluated. The comprehensive HLA analysis included the class I (A, B, C) and II (DRB1, DQA1, DQB1, DPA1, DPB1) loci. Most (>66%) of the predominantly Caucasian study population carried one or two of five to seven common alleles at each HLA locus. In spite of this limited diversity, 29% of the six of six antigen-matched transplants carried allele mismatches at HLA-A, -B, and/or -DRB1, and 92% carried at least one allele mismatch at one of the eight HLA loci tested. Of the 968 HLA-A,-B,-DRB1 allele-matched pairs, 89% carried mismatches at other HLA loci, predominantly at DP loci. The substantially greater than expected HLA allelic disparity between donor and recipient suggests extensive haplotypic diversity and underscores the importance of enhancing approaches to mitigate the deleterious effect of HLA mismatches.

Original language	English (US)
Pages (from-to)	30-40
Number of pages	11
Journal	Human Immunology
Volume	68
Issue number	1
DOIs	https://doi.org/10.1016/j.humimm.2006.09.004
State	Published - Jan 2007

Bibliographical note

Funding Information:
This work was supported by funding from the Office of Naval Research (N00014-93-1-0658, N00014-95-1-0055, N00014-96-2-0016) and Health Resources and Services Administration (240-97-0036), (National Marrow Donor Program) and the Office of Naval Research (N00014-94-1-0049, N00014-99-1-0551), (C. K. Hurley Research Program). We would like to acknowledge the assistance of the NMDP transplant and donor centers in providing cells and data for this study, Delene Johnson and her staff at the Blood Centers of the Pacific-Irwin Center for providing repository samples for analysis, the technical staff at the HLA typing laboratories, past participants in this retrospective study, and NMDP personnel including Michael Diko, Rose Fritz, Kenneth Bengtsson, Martin Maiers, and Penny Sinner for their assistance with the HLA typing and data analysis. Assistance with the design of the study was provided by Bo Dupont and helpful comments were provided by the NMDP Histocompatibility Committee.

Keywords

Bone marrow transplantation
HLA

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Hurley, C. K., Fernandez-Vina, M., Hildebrand, W. H., Noreen, H. J., Trachtenberg, E., Williams, T. M., Baxter-Lowe, L. A., Begovich, A. B., Petersdorf, E., Selvakumar, A., Stastny, P., Hegland, J., Hartzman, R. J., Carston, M., Gandham, S., Kollman, C., Nelson, G., Spellman, S., & Setterholm, M. (2007). A High Degree of HLA Disparity Arises From Limited Allelic Diversity: Analysis of 1775 Unrelated Bone Marrow Transplant Donor-Recipient Pairs. Human Immunology, 68(1), 30-40. https://doi.org/10.1016/j.humimm.2006.09.004

Hurley, CK, Fernandez-Vina, M, Hildebrand, WH, Noreen, HJ, Trachtenberg, E, Williams, TM, Baxter-Lowe, LA, Begovich, AB, Petersdorf, E, Selvakumar, A, Stastny, P, Hegland, J, Hartzman, RJ, Carston, M, Gandham, S, Kollman, C, Nelson, G, Spellman, S & Setterholm, M 2007, 'A High Degree of HLA Disparity Arises From Limited Allelic Diversity: Analysis of 1775 Unrelated Bone Marrow Transplant Donor-Recipient Pairs', Human Immunology, vol. 68, no. 1, pp. 30-40. https://doi.org/10.1016/j.humimm.2006.09.004

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abstract = "The allelic diversity and associated human leukocyte antigen (HLA) disparity of 1775 bone marrow recipients and their unrelated donors, matched for six of six (1361/1775,77%), five of six (397/1775, 22%), or four of six (17/1775, 1%) HLA-A, -B, -DR antigens, were retrospectively evaluated. The comprehensive HLA analysis included the class I (A, B, C) and II (DRB1, DQA1, DQB1, DPA1, DPB1) loci. Most (>66%) of the predominantly Caucasian study population carried one or two of five to seven common alleles at each HLA locus. In spite of this limited diversity, 29% of the six of six antigen-matched transplants carried allele mismatches at HLA-A, -B, and/or -DRB1, and 92% carried at least one allele mismatch at one of the eight HLA loci tested. Of the 968 HLA-A,-B,-DRB1 allele-matched pairs, 89% carried mismatches at other HLA loci, predominantly at DP loci. The substantially greater than expected HLA allelic disparity between donor and recipient suggests extensive haplotypic diversity and underscores the importance of enhancing approaches to mitigate the deleterious effect of HLA mismatches.",

keywords = "Bone marrow transplantation, HLA",

author = "Hurley, {Carolyn Katovich} and Marcelo Fernandez-Vina and Hildebrand, {William H.} and Noreen, {Harriet J.} and Elizabeth Trachtenberg and Williams, {Thomas M.} and Baxter-Lowe, {Lee Ann} and Begovich, {Ann B.} and Effie Petersdorf and Annamalai Selvakumar and Peter Stastny and Janet Hegland and Hartzman, {Robert J.} and Michael Carston and Sharavi Gandham and Craig Kollman and Gene Nelson and Stephen Spellman and Michelle Setterholm",

note = "Funding Information: This work was supported by funding from the Office of Naval Research (N00014-93-1-0658, N00014-95-1-0055, N00014-96-2-0016) and Health Resources and Services Administration (240-97-0036), (National Marrow Donor Program) and the Office of Naval Research (N00014-94-1-0049, N00014-99-1-0551), (C. K. Hurley Research Program). We would like to acknowledge the assistance of the NMDP transplant and donor centers in providing cells and data for this study, Delene Johnson and her staff at the Blood Centers of the Pacific-Irwin Center for providing repository samples for analysis, the technical staff at the HLA typing laboratories, past participants in this retrospective study, and NMDP personnel including Michael Diko, Rose Fritz, Kenneth Bengtsson, Martin Maiers, and Penny Sinner for their assistance with the HLA typing and data analysis. Assistance with the design of the study was provided by Bo Dupont and helpful comments were provided by the NMDP Histocompatibility Committee.",

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AU - Fernandez-Vina, Marcelo

AU - Hildebrand, William H.

AU - Noreen, Harriet J.

AU - Trachtenberg, Elizabeth

AU - Williams, Thomas M.

AU - Baxter-Lowe, Lee Ann

AU - Begovich, Ann B.

AU - Petersdorf, Effie

AU - Selvakumar, Annamalai

AU - Stastny, Peter

AU - Hegland, Janet

AU - Hartzman, Robert J.

AU - Carston, Michael

AU - Gandham, Sharavi

AU - Kollman, Craig

AU - Nelson, Gene

AU - Spellman, Stephen

AU - Setterholm, Michelle

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A High Degree of HLA Disparity Arises From Limited Allelic Diversity: Analysis of 1775 Unrelated Bone Marrow Transplant Donor-Recipient Pairs

Abstract

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Keywords

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