A review of HLA matching to improve clinical outcome in bone marrow transplants and the role of haplotyping in unrelated donor transplants
Main Article Content
Abstract
When the first allogeneic bone marrow transplants in humans was attempted, little was known of the major histocompatibility complex (HLA) and its role in ensuring success of the graft. Therefore, many of the early attempts resulted in failure. During the 1970s just a small number of alleles were detected serologically and the mixed lymphocyte reaction (MLR) served as a surrogate for class II matching, the DR series of alleles not being formally serologically defined until 1978. Nevertheless, selection of nuclear family members who were two HLA haplotype matched became possible using serology and the MLR and transplant successes were reported.
The breakthrough in technology was undoubtedly the introduction of DNA techniques, particularly DNA sequencing. This enabled fully matched unrelated individuals to be found as potential bone marrow donors. Genetic phasing or haplotyping of unrelated donors who are found on bone marrow registries has remained elusive until recently. The development of individual chromosome sequencing will permit haplotype matching in the absence of family studies and will expedite studies aimed at identifying other genes which are important matching factors.
AIM: The aim of this review is to outline the technological advances that have been made in HLA genotyping over the last 50 years. The progress from serology to DNA sequence as part of the matching algorithm is one of the reasons clinical results have improved so much during this period. This review outlines the DNA techniques that have been utilised for this purpose, concluding with a discussion of the value of haplotype matching in unrelated donor transplants, where the donor has been sourced from a bone marrow registry. Haplotype matching represents one of the last remaining hurdles to be overcome in unrelated donor bone marrow transplants.
Article Details
How to Cite
TAIT, Brian D.
A review of HLA matching to improve clinical outcome in bone marrow transplants and the role of haplotyping in unrelated donor transplants.
Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4723>. Date accessed: 23 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i11.4723.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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4. Elion G.B, Burgi, E., Hitchings G.H., et al. “Studies on Condensed Pyrimidine Systems. IX. The Synthesis of some 6-Substituted Purines.” Journal of the American Chemical Society, 1952; 74(2): 411–414.
https://doi.org/10.1021/ja01122a037
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6. Mathé Thé G., Amiel, J.L., Schwarzenberg, L., Cattan, A., Schneider, M., De Vries, M.J. et al. Successful Allogenic Bone Marrow Transplantation in Man: Chimerism, Induced Specific Tolerance and Possible Anti-Leukemic Effects. Blood, 1965;25(2):179–196.
7. Matsukura, M., Mery, A.M., Amiel, J.L. and Mathé, G. Investigation on a test of compatibility for allogeneic grafts. Transplantation, 1963; 1(1):.61–64.
8. Gatti, R.A., Meuwissen, H.J., Allen, H.D., Hong, R. and Good, R.A. Immunological reconstitution of sex-linked lymphopenic immunological deficiency The Lancet, 1968; 292(7583):1366–1369. https://www.sciencedirect.com/science/article/pii/S0140673668926731.
9. Buckner, C.D., Epstein, R.B., Rudolph, R.H., Clift, R.A., Storb, R. and Thomas, E.D. Allogeneic Marrow Engraftment Following Whole Body Irradiation in a Patient with Leukemia. Blood, 1970; 35(6):741–750.
10. Bach, Fritz H., Albertini, Richard J., Joo, P., Anderson, James L. and Bortin, Mortimer M. Bone marrow transplantation in a patient with Wiskott-Aldrich syndrome. The Lancet, 1968; 292(7583):1364–1366.
11. Bach, F.H., Albertini, R.J., Joo, P., Anderson, J.L. and Bortin, M.M. Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome. Transplantation, 1969; 8(4):510.
12. Meuwissen, H.J., Bortin, M.M., Bach, F.H., Porter, I.H., Schreinmachers, D., Harrison, B.A. and Taft, E. Long-term survival after bone marrow transplantation: A 15-year follow-up report of a patient with Wiskott-Aldrich syndrome. The Journal of Paediatrics, 1984; 105(3):365–369.
13. Glucksberg, H., Storb, R., Fefer, A., Buckner, C.D., Neiman, P.E., Clift, R.A. et al. Clinical manifestations of Graft-versus Host disease in human recipients of marrow from HL-A matched sibling donors. Transplantation, 1974; 18(4): 295–304.
14. Dausset J. Proposal for a world bank of reactive cells from bone marrow. Transplantation Proceedings, 1974; 6 (4): 429-430.
15. Kohonen-Corish, M.R.J. and Serjeantson, S.W. HLA-DRβ gene DNA polymorphisms revealed by Taq I correlate with HLA-DR specificities. Human Immunology, 1986; 15(3): 263–271.
16. Howell, W., Evans, P., Spellerberg, M.,
Wilson, P. and Smith, J. A comparison of serological, cellular and DNA-RFLP methods for HLA matching in the selection of related bone marrow donors. Bone Marrow Transplantation. 1989; 4(1): 63-68.
17. Pollack M.S, Chin-Louie J, Callaway, C., Blanco, M.A., Slavin, K., Sullivan, K. et al. Mixed Lymphocyte Reactions for Individuals with Phenotypic Identity for Specific HLA-B, DR Determinants: The Role of Linkage Disequilibrium and of Specific DR and Other Class II Determinants. Journal of Clinical Immunology, 1983; 3(4): 341–351. https://doi.org/10.1007/bf00915795.
18. Smith RA, Belcher R. Disparity in HLA-DR Typing and Mixed Lymphocyte Culture Reactivity. Annals of Laboratory and Clinical Science. 1987; 17 (5): 318 – 323.
19. Mullis, K., Faloona, F., Scharf, S., Saiki, R., Horn, G. and Erlich, H. Specific enzymatic amplification of DNA In Vitro: The polymerase chain reaction. Cold Spring Harbor Symposia on Quantitative Biology,1985; 51:263-273
20. Higuchi, R., von Beroldingen, C.H., Sensabaugh, G.F. and Erlich, H.A. DNA typing from single hairs. Nature, 1988; 332(6164): 543–546.
21. Westwood, S.A. and Werrett, D.J. An evaluation of the polymerase chain reaction method for forensic applications. Forensic Science International, 1990; 45(3): 201–21.
22. Levinson, G., Keyvanfar, K., Wu, J.C., Fugger, E.F., Fields, R.A., Harton, G.L., Palmer, F.T., Sisson, M.E., Starr, K.M., Dennison-Lagos, L., Calvo, L., Sherins, R.J., Bick, D., Schulman, J.D. and Black, S.H. DNA-based X-enriched sperm separation as an adjunct to preimplantation genetic testing for the prevention of X-linked disease. Molecular Human Reproduction, 1995; 1(2): 59–62.
23. De, B.K. and Srinivasan, A. Multiple primer pairs for the detection of HTLV-I by PCR. Nucleic Acids Research, 1989;17(5): 2142–2142.
doi:10.1093/nar/17.5.2142.
24. Rolfs, A., Schumacher, HC, and Marx., P.(eds). PCR topics: usage of polymerase chain reaction in genetic and infectious diseases. 1991, Berlin; New York: Springer-Verlag.
25. Kobayashi, T., Yokoyama, I, Uchida K, Tominaga, Y., Inoko, H., Tsuji, K. et al. The significance of HLA-DRB1 matching in clinical renal transplantation. Transplantation, 1992; 54 (2): 238–241.
https://doi.org/10.1097/00007890-199208000-00009
26. Nomura, N., Ota, M., Kato, S., Inoko, H. and Tsuji, K. Severe acute graft-versus-host disease by HLA-DPB1 disparity in recombinant family of bone marrow transplantation between serologically HLA-identical siblings: An application of the polymerase chain reaction—restriction fragment length polymorphism method. Human Immunology, 1991; 32(4): 261–268.
27. Ivinson, A.J. Optimizing PCR conditions for HLA class II SSO typing. European Journal of Immunogenetics, 1991;18(1–2): 23–32.
28. Verduyn, W., Doxiadis, I.I.N., Anholts, J., Drabbels, J.J.M., Naipal, A., D’Amaro, J., Persijn, G.G., Giphart, M.J. and Schreuder, G.M.Th. Biotinylated DRB sequence -specific oligonucleotides. Comparison to Serologic HLA-DR typing of Organ Donors in Eurotransplant.
Human Immunology, 1993; 37(1): 59-67.
29. Buyse, I., Decorte, R., Baens, M., Cuppens, H., Semana, G., Emonds, M.-P., Marynen, P. and Cassiman, J.-J. Rapid DNA typing of class II HLA antigens using the polymerase chain reaction and reverse dot blot hybridization. Tissue Antigens, 1993;41(1): 1–14.
30. Jordan, F., McWhinnie, A.J., Turner, S., Gavira, N., Calvert, A.A., Cleaver, S.A., Holman, R.H., Goldman, J.M. and Madrigal, J.A. Comparison of HLA-DRB1 typing by DNA-RFLP, PCR-SSO and PCR-SSP methods and their application in providing matched unrelated donors for bone marrow transplantation. Tissue Antigens, 1995; 45(2): 103–110.
31. Spurkland, A., Knutsen, I., Markussen, G., Vartdal, F., Egeland, T. and Thorsby, E. HLA matching of unrelated bone marrow transplant pairs: Direct sequencing of in vitro amplified HLA-DRB1 and -DQB1 genes using magnetic beads as solid support. Tissue Antigens, 1993; 41(3): 155–164.
32. Petersdorf, E.W., Malkki, M., Hsu, K., Bardy, P., Cesbron, A., Dickinson, A., Dubois, V., Fleischhauer, K., Kawase, T., Madrigal, A., Morishima, Y., Shaw, B., Spellman, S., Spierings, E., Stern, M., Tiercy, J.-M., Velardi, A. and Gooley, T. 16th IHIW: International Histocompatibility Working Group in Hematopoietic Cell Transplantation. International Journal of Immunogenetics, 2013; 40: 2-10.
33. Christiansen, F.T., Tay, G., Smith, L.K., Witt, C.S., Petersdorf, E.W., Bradley, B. and Dawkins, R.L. Histocompatibility matching for bone marrow transplantation donor-recipient pairs in the 4AOHW cell panel. Human Immunology, 1993; 38(1): 42-51.
34. Tay, GK., Witt, CS., Christiansen, FT., et al.
Matching for MHC Haplotypes results in improved
survival following unrelated bone Marrow
transplantation. Bone Marrow Transplantation.
1995;15(3): 381-385.
35. Tay GK, Witt CS, Christiansen FT, Corbett
JM, Dawkins RL. The identification of MHC
Identical siblings without HLA typing. Exp.
Hematol.1995;23(14): 1655-1660.
36. Witt, C., Moghaddam, P. Hanifi., van der Meer,
R., Trimboli, F. Ottinger, H., Christiansen, F. and
Giphart, M. Matching for TNF microsatellites
Is strongly associated with matching for other
non-HLA MHC sequences in unrelated bone
marrow donor-recipient pairs. Human
Immunology, 1999; 60(9): 862–866.
37. Witt, C., Sayer, D., Trimboli, F., Saw, M., Herrmann, R., Cannell, P., Baker, D. and Christiansen, F. Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome. Human Immunology, 2000; 61(2): 85–91.
38. Kitcharoen, K., Witt, C.S., Romphruk, A.V., Christiansen, F.T. and Leelayuwat, C. MICA, MICB, and MHC Beta Block Matching in Bone Marrow Transplantation: Relevance to Transplantation Outcome. Human Immunology,2006; 67(3): 238–246.
39. Malkki, M., Single, R., Carrington, M., Thomson, G. and Petersdorf,E MHC microsatellite diversity and linkage disequilibrium among common HLA-A, HLA-B, DRB1 haplotypes: implications for unrelated donor hematopoietic transplantation and disease association studies. Tissue Antigens, 2005; 66(2): 114–124.
40. Guo, Z., Hood, L., Malkki, M. and Petersdorf, E.W. Long-range multilocus haplotype phasing of the MHC. Proceedings of the National Academy of Sciences, 2006;103(18): 6964–6969.
41. Petersdorf, Effie W, Malki, M., Gooley, T.A., et al. MHC Haplotype Matching for Z PLoS Medicine, 2007; 4(1): 59-68.
https://doi.org/10.1371/journal.pmed.0040008.
42. Tait, B.D. The importance of establishing genetic phase in clinical medicine. International Journal of Immunogenetics, 2022; 49(1): 1–7.
doi:10.1182/blood-2004-07-2717.
2. Dausset, J. Iso-Leuko-Antibodies. Vox Sanguinis, 1958;3(1): 40–41.
3. Goodwin, L. George Hitchings and Gertrude Elion-Nobel Prize Winners. Parasitology Today, 1989;5(2):33.
4. Elion G.B, Burgi, E., Hitchings G.H., et al. “Studies on Condensed Pyrimidine Systems. IX. The Synthesis of some 6-Substituted Purines.” Journal of the American Chemical Society, 1952; 74(2): 411–414.
https://doi.org/10.1021/ja01122a037
5. Epstein, R.B., Storb, R., Ragde, H. and Thomas, E.D. Cytotoxic typing antisera for marrow grafting in littermate dog. Transplantation, 1968; 6(1):45–58.
6. Mathé Thé G., Amiel, J.L., Schwarzenberg, L., Cattan, A., Schneider, M., De Vries, M.J. et al. Successful Allogenic Bone Marrow Transplantation in Man: Chimerism, Induced Specific Tolerance and Possible Anti-Leukemic Effects. Blood, 1965;25(2):179–196.
7. Matsukura, M., Mery, A.M., Amiel, J.L. and Mathé, G. Investigation on a test of compatibility for allogeneic grafts. Transplantation, 1963; 1(1):.61–64.
8. Gatti, R.A., Meuwissen, H.J., Allen, H.D., Hong, R. and Good, R.A. Immunological reconstitution of sex-linked lymphopenic immunological deficiency The Lancet, 1968; 292(7583):1366–1369. https://www.sciencedirect.com/science/article/pii/S0140673668926731.
9. Buckner, C.D., Epstein, R.B., Rudolph, R.H., Clift, R.A., Storb, R. and Thomas, E.D. Allogeneic Marrow Engraftment Following Whole Body Irradiation in a Patient with Leukemia. Blood, 1970; 35(6):741–750.
10. Bach, Fritz H., Albertini, Richard J., Joo, P., Anderson, James L. and Bortin, Mortimer M. Bone marrow transplantation in a patient with Wiskott-Aldrich syndrome. The Lancet, 1968; 292(7583):1364–1366.
11. Bach, F.H., Albertini, R.J., Joo, P., Anderson, J.L. and Bortin, M.M. Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome. Transplantation, 1969; 8(4):510.
12. Meuwissen, H.J., Bortin, M.M., Bach, F.H., Porter, I.H., Schreinmachers, D., Harrison, B.A. and Taft, E. Long-term survival after bone marrow transplantation: A 15-year follow-up report of a patient with Wiskott-Aldrich syndrome. The Journal of Paediatrics, 1984; 105(3):365–369.
13. Glucksberg, H., Storb, R., Fefer, A., Buckner, C.D., Neiman, P.E., Clift, R.A. et al. Clinical manifestations of Graft-versus Host disease in human recipients of marrow from HL-A matched sibling donors. Transplantation, 1974; 18(4): 295–304.
14. Dausset J. Proposal for a world bank of reactive cells from bone marrow. Transplantation Proceedings, 1974; 6 (4): 429-430.
15. Kohonen-Corish, M.R.J. and Serjeantson, S.W. HLA-DRβ gene DNA polymorphisms revealed by Taq I correlate with HLA-DR specificities. Human Immunology, 1986; 15(3): 263–271.
16. Howell, W., Evans, P., Spellerberg, M.,
Wilson, P. and Smith, J. A comparison of serological, cellular and DNA-RFLP methods for HLA matching in the selection of related bone marrow donors. Bone Marrow Transplantation. 1989; 4(1): 63-68.
17. Pollack M.S, Chin-Louie J, Callaway, C., Blanco, M.A., Slavin, K., Sullivan, K. et al. Mixed Lymphocyte Reactions for Individuals with Phenotypic Identity for Specific HLA-B, DR Determinants: The Role of Linkage Disequilibrium and of Specific DR and Other Class II Determinants. Journal of Clinical Immunology, 1983; 3(4): 341–351. https://doi.org/10.1007/bf00915795.
18. Smith RA, Belcher R. Disparity in HLA-DR Typing and Mixed Lymphocyte Culture Reactivity. Annals of Laboratory and Clinical Science. 1987; 17 (5): 318 – 323.
19. Mullis, K., Faloona, F., Scharf, S., Saiki, R., Horn, G. and Erlich, H. Specific enzymatic amplification of DNA In Vitro: The polymerase chain reaction. Cold Spring Harbor Symposia on Quantitative Biology,1985; 51:263-273
20. Higuchi, R., von Beroldingen, C.H., Sensabaugh, G.F. and Erlich, H.A. DNA typing from single hairs. Nature, 1988; 332(6164): 543–546.
21. Westwood, S.A. and Werrett, D.J. An evaluation of the polymerase chain reaction method for forensic applications. Forensic Science International, 1990; 45(3): 201–21.
22. Levinson, G., Keyvanfar, K., Wu, J.C., Fugger, E.F., Fields, R.A., Harton, G.L., Palmer, F.T., Sisson, M.E., Starr, K.M., Dennison-Lagos, L., Calvo, L., Sherins, R.J., Bick, D., Schulman, J.D. and Black, S.H. DNA-based X-enriched sperm separation as an adjunct to preimplantation genetic testing for the prevention of X-linked disease. Molecular Human Reproduction, 1995; 1(2): 59–62.
23. De, B.K. and Srinivasan, A. Multiple primer pairs for the detection of HTLV-I by PCR. Nucleic Acids Research, 1989;17(5): 2142–2142.
doi:10.1093/nar/17.5.2142.
24. Rolfs, A., Schumacher, HC, and Marx., P.(eds). PCR topics: usage of polymerase chain reaction in genetic and infectious diseases. 1991, Berlin; New York: Springer-Verlag.
25. Kobayashi, T., Yokoyama, I, Uchida K, Tominaga, Y., Inoko, H., Tsuji, K. et al. The significance of HLA-DRB1 matching in clinical renal transplantation. Transplantation, 1992; 54 (2): 238–241.
https://doi.org/10.1097/00007890-199208000-00009
26. Nomura, N., Ota, M., Kato, S., Inoko, H. and Tsuji, K. Severe acute graft-versus-host disease by HLA-DPB1 disparity in recombinant family of bone marrow transplantation between serologically HLA-identical siblings: An application of the polymerase chain reaction—restriction fragment length polymorphism method. Human Immunology, 1991; 32(4): 261–268.
27. Ivinson, A.J. Optimizing PCR conditions for HLA class II SSO typing. European Journal of Immunogenetics, 1991;18(1–2): 23–32.
28. Verduyn, W., Doxiadis, I.I.N., Anholts, J., Drabbels, J.J.M., Naipal, A., D’Amaro, J., Persijn, G.G., Giphart, M.J. and Schreuder, G.M.Th. Biotinylated DRB sequence -specific oligonucleotides. Comparison to Serologic HLA-DR typing of Organ Donors in Eurotransplant.
Human Immunology, 1993; 37(1): 59-67.
29. Buyse, I., Decorte, R., Baens, M., Cuppens, H., Semana, G., Emonds, M.-P., Marynen, P. and Cassiman, J.-J. Rapid DNA typing of class II HLA antigens using the polymerase chain reaction and reverse dot blot hybridization. Tissue Antigens, 1993;41(1): 1–14.
30. Jordan, F., McWhinnie, A.J., Turner, S., Gavira, N., Calvert, A.A., Cleaver, S.A., Holman, R.H., Goldman, J.M. and Madrigal, J.A. Comparison of HLA-DRB1 typing by DNA-RFLP, PCR-SSO and PCR-SSP methods and their application in providing matched unrelated donors for bone marrow transplantation. Tissue Antigens, 1995; 45(2): 103–110.
31. Spurkland, A., Knutsen, I., Markussen, G., Vartdal, F., Egeland, T. and Thorsby, E. HLA matching of unrelated bone marrow transplant pairs: Direct sequencing of in vitro amplified HLA-DRB1 and -DQB1 genes using magnetic beads as solid support. Tissue Antigens, 1993; 41(3): 155–164.
32. Petersdorf, E.W., Malkki, M., Hsu, K., Bardy, P., Cesbron, A., Dickinson, A., Dubois, V., Fleischhauer, K., Kawase, T., Madrigal, A., Morishima, Y., Shaw, B., Spellman, S., Spierings, E., Stern, M., Tiercy, J.-M., Velardi, A. and Gooley, T. 16th IHIW: International Histocompatibility Working Group in Hematopoietic Cell Transplantation. International Journal of Immunogenetics, 2013; 40: 2-10.
33. Christiansen, F.T., Tay, G., Smith, L.K., Witt, C.S., Petersdorf, E.W., Bradley, B. and Dawkins, R.L. Histocompatibility matching for bone marrow transplantation donor-recipient pairs in the 4AOHW cell panel. Human Immunology, 1993; 38(1): 42-51.
34. Tay, GK., Witt, CS., Christiansen, FT., et al.
Matching for MHC Haplotypes results in improved
survival following unrelated bone Marrow
transplantation. Bone Marrow Transplantation.
1995;15(3): 381-385.
35. Tay GK, Witt CS, Christiansen FT, Corbett
JM, Dawkins RL. The identification of MHC
Identical siblings without HLA typing. Exp.
Hematol.1995;23(14): 1655-1660.
36. Witt, C., Moghaddam, P. Hanifi., van der Meer,
R., Trimboli, F. Ottinger, H., Christiansen, F. and
Giphart, M. Matching for TNF microsatellites
Is strongly associated with matching for other
non-HLA MHC sequences in unrelated bone
marrow donor-recipient pairs. Human
Immunology, 1999; 60(9): 862–866.
37. Witt, C., Sayer, D., Trimboli, F., Saw, M., Herrmann, R., Cannell, P., Baker, D. and Christiansen, F. Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome. Human Immunology, 2000; 61(2): 85–91.
38. Kitcharoen, K., Witt, C.S., Romphruk, A.V., Christiansen, F.T. and Leelayuwat, C. MICA, MICB, and MHC Beta Block Matching in Bone Marrow Transplantation: Relevance to Transplantation Outcome. Human Immunology,2006; 67(3): 238–246.
39. Malkki, M., Single, R., Carrington, M., Thomson, G. and Petersdorf,E MHC microsatellite diversity and linkage disequilibrium among common HLA-A, HLA-B, DRB1 haplotypes: implications for unrelated donor hematopoietic transplantation and disease association studies. Tissue Antigens, 2005; 66(2): 114–124.
40. Guo, Z., Hood, L., Malkki, M. and Petersdorf, E.W. Long-range multilocus haplotype phasing of the MHC. Proceedings of the National Academy of Sciences, 2006;103(18): 6964–6969.
41. Petersdorf, Effie W, Malki, M., Gooley, T.A., et al. MHC Haplotype Matching for Z PLoS Medicine, 2007; 4(1): 59-68.
https://doi.org/10.1371/journal.pmed.0040008.
42. Tait, B.D. The importance of establishing genetic phase in clinical medicine. International Journal of Immunogenetics, 2022; 49(1): 1–7.