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ARTICLE |

HLA Typing for Bone Marrow Transplantation: Title and subTitle BreakNew Polymerase Chain Reaction—Based Methods FREE

Ann B. Begovich, PhD; Henry A. Erlich, PhD
[+] Author Affiliations

Reprint requests to Department of Human Genetics, Roche Molecular Systems Inc, 1145 Atlantic Ave, Alameda, CA 94501 (Dr Begovich).

Toward Optimal Laboratory Use section editor: George D. Lundberg, MD, Editor, JAMA.


JAMA. 1995;273(7):586-591. doi:10.1001/jama.1995.03520310084034
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Published online

BONE MARROW transplantation, first introduced into clinical practice in the 1960s, has now become an accepted form of therapy for a variety of hematologic malignancies as well as a number of other cancers, inherited blood disorders, immunodeficiency syndromes, and certain metabolic diseases.1,2 In general, the purpose of bone marrow transplantation is to (1) replace malignant or genetically defective hematopoietic stem cells with healthy, fully functional stem cells; (2) allow the cancer patient to survive the high-dose radiation and/or chemotherapy required to destroy the malignant cells; and (3) in the case of certain cancers, provide a source of immunocompetent cells that can destroy any residual malignant cells (graft vs leukemia effect).3-5 The clinical procedure of bone marrow transplantation involves the destruction of the patient's own marrow by irradiation and/or chemotherapy followed by the infusion of healthy bone marrow obtained from another individual (an allogeneic transplant). In cases of solid

REFERENCES

Forman SJ, Blume KG, Thomas ED, eds. Bone Marrow Transplantation . Boston, Mass: Blackwell Scientific Publications Inc; 1994;.
Clift RA, Storb R.  Histoincompatible bone marrow transplants in humans. Annu Rev Immunol . 1987;;5:43-64.
Bortin M, Rimm A, Saltzstein E.  Graft versus leukemia: quantification of adoptive immunotherapy in murine leukemia. Science . 1973;;179:811-813.
Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED.  Antileukemic effect of chronic graftversus-host disease. N Engl J Med . 1981;;304:1529-1533.
Sullivan KM, Weiden PL, Storb R, et al.  Influence of acute and chronic graft versus host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood . 1989;; 73:1720-1728.
Barnes DWH, Loutit JF.  Spleen protection: the cellular hypothesis.  In: Bacq ZM, Alexander P, eds. Radiology Symposium 1954 . London, England: Butterworths; 1955;:134.
Uphoff DE.  Genetic factors influencing irradiation protection by bone marrow, I: the Fl hybrid effect. J Natl Cancer Inst . 1957;;19:123-130.
Uphoff DE, Law LW.  Genetic factors influencing irradiation protection by bone marrow, II: the histocompatibility-2 (H-2) locus. J Natl Cancer Inst . 1958;;20:617-624.
Dausset J.  Iso-leuco-anticorps. Acta Haematol . 1958;;20:156-166.
Amos DB, Bashir H, Boyle W, MacQueen M, Tiilikainen A.  A simple microcytotoxicity test. Transplantation . 1969;;7:220-223.
Bach FH, Voynow NK.  One-way stimulation in mixed leukocyte cultures. Science . 1966;;153:545-547.
Dupont B.  HLA factors and bone marrow grafting.  In: Burchenal JH, Oettgen HF, eds. Cancer: Achievements, Challenges and Prospects for the 1980s . New York, NY: Grune & Stratton; 1980;: 683-693.
Zemmour J, Parham P.  HLA class I nucleotide sequences, 1992. Tissue Antigens . 1992;;40:221-228.
Bodmer JG, Marsh SGE, Albert ED, et al.  Nomenclature for factors of the HLA system, 1994. Tissue Antigens . 1994;;44:1-18.
Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC.  Structure of the human class I histocompatibility antigen, HLA-A2. Nature . 1987;;329:506-512.
Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC.  The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature . 1987;;329:512-518.
Garrett TPJ, Saper MA, Bjorkman PJ, Strominger JL, Wiley DC.  Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature . 1989;;342:692-696.
Madden DR, Gorga JC, Strominger JL, Wiley DC.  The three-dimensional structure of HLA-B27 at 2.1: a resolution suggests a general mechanism for tight peptide binding to MHC. Cell . 1992;;70: 1035-1048.
Marsh SGE, Bodmer JG.  HLA class II nucleotide sequences, 1992. Tissue Antigens . 1992;;40229-243.
Brown JH, Jardetzky TS, Gorga JC, et al.  Threedimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature . 1993;;364: 33-39.
Doherty PC, Zinkernagel RM.  A biological role for the major histocompatibility antigens. Lancet . 1975;;1:1406-1409.
Hill AVS, Allsopp CEM, Kwiatkowski D, et al.  Common West African HLA antigens are associated with protection from severe malaria. Nature . 1991;;352:595-600.
Terasaki PI, Mandell M, Van de Water J, Edgington TE.  Human blood lymphocyte cytotoxicity reactions with allogeneic antisera. Ann N Y Acad Sci . 1964;;120:322-334.
Flomenberg N.  Functional polymorphisms of HLA class II gene products detected by T-lymphocyte clones: summary of the Tenth International Histocompatibility Workshop Cellular Studies.  In: Dupont B, ed. Immunobiology of HLA, Volume 1: Histocompatibility Testing, 1987 . New York: Springer-Verlag NY Inc; 1989;:532-550.
Mickelson EM, Bartsch GE, Hansen JA, Dupont B.  The MLC assay as a test for HLA-D region compatibility between patients and unrelated donors: results of a national marrow donor program involving multiple centers. Tissue Antigens . 1993;; 42:465-472.
Beatty PG, Anasetti C, Hansen JA, et al.  Marrow transplantation from unrelated donors for treatment of hematologic malignancies: effect of mismatching for one HLA locus. Blood . 1993;;81:249-253.
McCullough J, Hansen JA, Perkins H, Stroncek D, Bartsch G.  Establishment of the National Bone Marrow Donor Registry.  In: Gale RP, Champlin RE, eds. Bone Marrow Transplantation: Current Controversies . New York, NY: Alan R Liss Inc; 1989;:641-658.
Storb R, Deeg HJ, Whitehead J, et al.  Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med . 1986;;314:729-735.
Wettstein PJ.  Minor histocompatibility loci.  In: Litwin SD, ed. Human Immunogenetics . New York, NY: Marcel Dekker Inc; 1989;:339-357.
Saiki RK, Gelfand DH, Stoffel S, et al.  Primerdirected enzymatic amplification of DNA with a thermostable DNA polymerase. Science . 1988;;239: 487-491.
Mullis KB, Faloona F.  Specific synthesis of DNA in vitro via polymerase catalyzed chain reaction. Methods Enzymol . 1987;;155:335-350.
Trowsdale J, Young JAT, Kelly AP, et al.  Structure, sequence, and polymorphism in the HLA-D region. Immunol Rev . 1985;;85:5-43.
Erlich HA, Sheldon EL, Horn G.  HLA typing using DNA probes. Biotechnology . 1986;;4:975-981.
Saiki RK, Bugawan TL, Horn GT, Mullis KB, Erlich HA.  Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele-specific oligonucleotide probes. Nature . 1986;;324:163-166.
Scharf SJ, Griffith RL, Erlich HA.  Rapid typing of DNA sequence polymorphism at the HLADRB1 locus using the polymerase chain reaction and nonradioactive oligonucleotide probes. Hum Immunol . 1991;;30:190-201.
Bugawan TL, Begovich AB, Erlich HA.  Rapid HLA-DPB typing using enzymatically amplified DNA and nonradioactive sequence specific oligonucleotide probes. Immunogenetics . 1990;;32:231-241.
Oh SH, Fleischhauer K, Yang SY.  Isoelectric focusing subtypes of HLA-A can be defined by oligonucleotide typing. Tissue Antigens . 1993;;41: 135-142.
Yoshida M, Kimura A, Numano F, Sasazuki T.  Polymerase-chain-reaction—based analysis of polymorphism in the HLA-B gene. Hum Immunol . 1992;;34:257-266.
Olerup O, Zetterquist H.  HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours: an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens . 1992;;39:225-235.
Newton CR, Graham A, Heptinstall LE, et al.  Analysis of any point mutation in DNA: the amplification refractory mutation system (ARMS). Nucleic Acids Res . 1989;;17:2503-2516.
Maeda M, Murayama N, Ishi H, et al.  A simple and rapid method for HLA-DQA1 genotyping by digestion of PCR-amplified DNA with allele specific restriction endonucleases. Tissue Antigens . 1989;;34:290-298.
Hoshino S, Kimura A, Fukuda Y, Dohi K, Sasazuki T.  Polymerase chain reaction-single-strand conformation polymorphism analysis of polymorphism in DPA1 and DPB1 genes: a simple, economical and rapid method for histocompatibility testing. Hum Immunol . 1992;;33:98-107.
Carrington M, Miller T, White M, et al.  Typing of HLA-DQA1 and DQB1 using DNA single-strand conformation polymorphism. Hum Immunol . 1992;; 33:208-212.
Zimmerman PA, Carrington MN, Nutman TB.  Exploiting structural differences among heteroduplex molecules to simplify genotyping the DQA1 and DQB1 alleles in human lymphocyte typing. Nucleic Acids Res . 1993;;21:4541-4547.
Saiki RK, Walsh PS, Levenson CH, Erlich HA.  Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes. Proc Natl Acad Sci U S A . 1989;;86:6230-6234.
Kawai S, Maekawajiri S, Tokunaga K, et al.  A simple method of HLA-DRB typing using enzymatically amplified DNA and immobilized probes on microtiter plate. Hum Immunol . 1994;;41:121-126.
Erlich H, Bugawan T, Begovich AB, et al.  HLADR, DQ, and DP typing using PCR amplification and immobilized probes. Eur J Immunogen . 1991;; 18:33-55.
Buyse I, Decorte R, Baens M, et al.  Rapid DNA typing of class II HLA antigens using the polymerase chain reaction and reverse dot blot hybridization. Tissue Antigens . 1993;;41:1-14.
NgJ, Hurley CK, Baxter-Lowe LA, et al.  Largescale oligonucleotide typing for HLA-DRB1/3/4 and HLA-DQB1 is highly accurate, specific, and reliable. Tissue Antigens . 1993;;42:473-479.
Bugawan TL, Apple R, Erlich HA.  A method for typing polymorphism at the HLA-A locus using PCR amplification and immobilized oligonucleotide probes. Tissue Antigens . 1994;;44:137-147.
Bugawan TL, Apple R, Erlich HA.  Population screening with a PCR/immobilized SSO probe HLA-A test reveals new HLA-A alleles. Hum Immunol . 1994;;40( (suppl 1) ):67. Abstract.
Petersdorf EW, Anasetti C, Martin PJ, Smith AG, Longton G, Hansen JA.  Effect of HLA-DRB1 and DQB1 allele disparity on the development of acute graft versus host disease following unrelated donor marrow transplantation. Human Immunol . 1994;;40( (suppl 1) ):3. Abstract.
Longo MC, Berninger MS, Hartley JL.  Use of uracil DNA glycosylase to control carry-over contamination in the polymerase chain reaction. Gene . 1990;;93:125-128.

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Forman SJ, Blume KG, Thomas ED, eds. Bone Marrow Transplantation . Boston, Mass: Blackwell Scientific Publications Inc; 1994;.
Clift RA, Storb R.  Histoincompatible bone marrow transplants in humans. Annu Rev Immunol . 1987;;5:43-64.
Bortin M, Rimm A, Saltzstein E.  Graft versus leukemia: quantification of adoptive immunotherapy in murine leukemia. Science . 1973;;179:811-813.
Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED.  Antileukemic effect of chronic graftversus-host disease. N Engl J Med . 1981;;304:1529-1533.
Sullivan KM, Weiden PL, Storb R, et al.  Influence of acute and chronic graft versus host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood . 1989;; 73:1720-1728.
Barnes DWH, Loutit JF.  Spleen protection: the cellular hypothesis.  In: Bacq ZM, Alexander P, eds. Radiology Symposium 1954 . London, England: Butterworths; 1955;:134.
Uphoff DE.  Genetic factors influencing irradiation protection by bone marrow, I: the Fl hybrid effect. J Natl Cancer Inst . 1957;;19:123-130.
Uphoff DE, Law LW.  Genetic factors influencing irradiation protection by bone marrow, II: the histocompatibility-2 (H-2) locus. J Natl Cancer Inst . 1958;;20:617-624.
Dausset J.  Iso-leuco-anticorps. Acta Haematol . 1958;;20:156-166.
Amos DB, Bashir H, Boyle W, MacQueen M, Tiilikainen A.  A simple microcytotoxicity test. Transplantation . 1969;;7:220-223.
Bach FH, Voynow NK.  One-way stimulation in mixed leukocyte cultures. Science . 1966;;153:545-547.
Dupont B.  HLA factors and bone marrow grafting.  In: Burchenal JH, Oettgen HF, eds. Cancer: Achievements, Challenges and Prospects for the 1980s . New York, NY: Grune & Stratton; 1980;: 683-693.
Zemmour J, Parham P.  HLA class I nucleotide sequences, 1992. Tissue Antigens . 1992;;40:221-228.
Bodmer JG, Marsh SGE, Albert ED, et al.  Nomenclature for factors of the HLA system, 1994. Tissue Antigens . 1994;;44:1-18.
Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC.  Structure of the human class I histocompatibility antigen, HLA-A2. Nature . 1987;;329:506-512.
Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC.  The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature . 1987;;329:512-518.
Garrett TPJ, Saper MA, Bjorkman PJ, Strominger JL, Wiley DC.  Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature . 1989;;342:692-696.
Madden DR, Gorga JC, Strominger JL, Wiley DC.  The three-dimensional structure of HLA-B27 at 2.1: a resolution suggests a general mechanism for tight peptide binding to MHC. Cell . 1992;;70: 1035-1048.
Marsh SGE, Bodmer JG.  HLA class II nucleotide sequences, 1992. Tissue Antigens . 1992;;40229-243.
Brown JH, Jardetzky TS, Gorga JC, et al.  Threedimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature . 1993;;364: 33-39.
Doherty PC, Zinkernagel RM.  A biological role for the major histocompatibility antigens. Lancet . 1975;;1:1406-1409.
Hill AVS, Allsopp CEM, Kwiatkowski D, et al.  Common West African HLA antigens are associated with protection from severe malaria. Nature . 1991;;352:595-600.
Terasaki PI, Mandell M, Van de Water J, Edgington TE.  Human blood lymphocyte cytotoxicity reactions with allogeneic antisera. Ann N Y Acad Sci . 1964;;120:322-334.
Flomenberg N.  Functional polymorphisms of HLA class II gene products detected by T-lymphocyte clones: summary of the Tenth International Histocompatibility Workshop Cellular Studies.  In: Dupont B, ed. Immunobiology of HLA, Volume 1: Histocompatibility Testing, 1987 . New York: Springer-Verlag NY Inc; 1989;:532-550.
Mickelson EM, Bartsch GE, Hansen JA, Dupont B.  The MLC assay as a test for HLA-D region compatibility between patients and unrelated donors: results of a national marrow donor program involving multiple centers. Tissue Antigens . 1993;; 42:465-472.
Beatty PG, Anasetti C, Hansen JA, et al.  Marrow transplantation from unrelated donors for treatment of hematologic malignancies: effect of mismatching for one HLA locus. Blood . 1993;;81:249-253.
McCullough J, Hansen JA, Perkins H, Stroncek D, Bartsch G.  Establishment of the National Bone Marrow Donor Registry.  In: Gale RP, Champlin RE, eds. Bone Marrow Transplantation: Current Controversies . New York, NY: Alan R Liss Inc; 1989;:641-658.
Storb R, Deeg HJ, Whitehead J, et al.  Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med . 1986;;314:729-735.
Wettstein PJ.  Minor histocompatibility loci.  In: Litwin SD, ed. Human Immunogenetics . New York, NY: Marcel Dekker Inc; 1989;:339-357.
Saiki RK, Gelfand DH, Stoffel S, et al.  Primerdirected enzymatic amplification of DNA with a thermostable DNA polymerase. Science . 1988;;239: 487-491.
Mullis KB, Faloona F.  Specific synthesis of DNA in vitro via polymerase catalyzed chain reaction. Methods Enzymol . 1987;;155:335-350.
Trowsdale J, Young JAT, Kelly AP, et al.  Structure, sequence, and polymorphism in the HLA-D region. Immunol Rev . 1985;;85:5-43.
Erlich HA, Sheldon EL, Horn G.  HLA typing using DNA probes. Biotechnology . 1986;;4:975-981.
Saiki RK, Bugawan TL, Horn GT, Mullis KB, Erlich HA.  Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele-specific oligonucleotide probes. Nature . 1986;;324:163-166.
Scharf SJ, Griffith RL, Erlich HA.  Rapid typing of DNA sequence polymorphism at the HLADRB1 locus using the polymerase chain reaction and nonradioactive oligonucleotide probes. Hum Immunol . 1991;;30:190-201.
Bugawan TL, Begovich AB, Erlich HA.  Rapid HLA-DPB typing using enzymatically amplified DNA and nonradioactive sequence specific oligonucleotide probes. Immunogenetics . 1990;;32:231-241.
Oh SH, Fleischhauer K, Yang SY.  Isoelectric focusing subtypes of HLA-A can be defined by oligonucleotide typing. Tissue Antigens . 1993;;41: 135-142.
Yoshida M, Kimura A, Numano F, Sasazuki T.  Polymerase-chain-reaction—based analysis of polymorphism in the HLA-B gene. Hum Immunol . 1992;;34:257-266.
Olerup O, Zetterquist H.  HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours: an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens . 1992;;39:225-235.
Newton CR, Graham A, Heptinstall LE, et al.  Analysis of any point mutation in DNA: the amplification refractory mutation system (ARMS). Nucleic Acids Res . 1989;;17:2503-2516.
Maeda M, Murayama N, Ishi H, et al.  A simple and rapid method for HLA-DQA1 genotyping by digestion of PCR-amplified DNA with allele specific restriction endonucleases. Tissue Antigens . 1989;;34:290-298.
Hoshino S, Kimura A, Fukuda Y, Dohi K, Sasazuki T.  Polymerase chain reaction-single-strand conformation polymorphism analysis of polymorphism in DPA1 and DPB1 genes: a simple, economical and rapid method for histocompatibility testing. Hum Immunol . 1992;;33:98-107.
Carrington M, Miller T, White M, et al.  Typing of HLA-DQA1 and DQB1 using DNA single-strand conformation polymorphism. Hum Immunol . 1992;; 33:208-212.
Zimmerman PA, Carrington MN, Nutman TB.  Exploiting structural differences among heteroduplex molecules to simplify genotyping the DQA1 and DQB1 alleles in human lymphocyte typing. Nucleic Acids Res . 1993;;21:4541-4547.
Saiki RK, Walsh PS, Levenson CH, Erlich HA.  Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes. Proc Natl Acad Sci U S A . 1989;;86:6230-6234.
Kawai S, Maekawajiri S, Tokunaga K, et al.  A simple method of HLA-DRB typing using enzymatically amplified DNA and immobilized probes on microtiter plate. Hum Immunol . 1994;;41:121-126.
Erlich H, Bugawan T, Begovich AB, et al.  HLADR, DQ, and DP typing using PCR amplification and immobilized probes. Eur J Immunogen . 1991;; 18:33-55.
Buyse I, Decorte R, Baens M, et al.  Rapid DNA typing of class II HLA antigens using the polymerase chain reaction and reverse dot blot hybridization. Tissue Antigens . 1993;;41:1-14.
NgJ, Hurley CK, Baxter-Lowe LA, et al.  Largescale oligonucleotide typing for HLA-DRB1/3/4 and HLA-DQB1 is highly accurate, specific, and reliable. Tissue Antigens . 1993;;42:473-479.
Bugawan TL, Apple R, Erlich HA.  A method for typing polymorphism at the HLA-A locus using PCR amplification and immobilized oligonucleotide probes. Tissue Antigens . 1994;;44:137-147.
Bugawan TL, Apple R, Erlich HA.  Population screening with a PCR/immobilized SSO probe HLA-A test reveals new HLA-A alleles. Hum Immunol . 1994;;40( (suppl 1) ):67. Abstract.
Petersdorf EW, Anasetti C, Martin PJ, Smith AG, Longton G, Hansen JA.  Effect of HLA-DRB1 and DQB1 allele disparity on the development of acute graft versus host disease following unrelated donor marrow transplantation. Human Immunol . 1994;;40( (suppl 1) ):3. Abstract.
Longo MC, Berninger MS, Hartley JL.  Use of uracil DNA glycosylase to control carry-over contamination in the polymerase chain reaction. Gene . 1990;;93:125-128.
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