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HLA Humoral Allosensitization

Clinical Significance of Humoral Allosensitization of HLA Antigens

  • Chapter
The HLA System

Abstract

HLA specific humoral sensitization presents a significant problem to patients considered for organ transplantation or platelet transfusion therapy. This alloimmunization can result from previous exposure to HLA antigens through blood transfusion, transplantation and pregnancy. Alloantibodies are usually determined by testing patient serum in complement-dependent lymphocytotoxicity assays against an HLA typed cell panel and the percentage of panel reactive antibody (PRA) indicates the degree of humoral sensitization of patients. Moreover, crossmatch assays of patient sera are generally necessary for the selection of appropriate donors.

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References

  1. Rodey GE and Fuller TC: Public Epitopes and the Antigenic Structure of the HLA Molecules, CRC Critical Reviews in Immunology 1987; 7:229–267.

    PubMed  CAS  Google Scholar 

  2. van Rood JJ and van Leeuwen A: Leukocyte Grouping: A Method and Its Application. J Clin Invest 1963; 42:1382.

    Article  Google Scholar 

  3. Ayres J and Cresswell P: HLA-B Specificities and w4/w6 Specificities Are On the Same Polypeptide. Eur J Immunol 1976; 6:794.

    Article  PubMed  CAS  Google Scholar 

  4. Parham P: Antigenic Determinants On the B7 Molecule; Bw6 and B7 Specific Determinants are Spatially Separate. Immunogenetics 1983; 18:1.

    Article  PubMed  CAS  Google Scholar 

  5. Rodey GE: Class I Antigens: HLA-A,-B,-C and Cross-Reactive Groups. In (Moulds JM et al, eds.) Scientific and Technical Aspects of the Major Histocompatibility Complex (AABB) 1989; 23–46.

    Google Scholar 

  6. Schwartz BD, Luehrman LK and Rodey GE: A Public Antigenic Determinant on a Family of HLA-B Molecules — A Basis for Crossreactivity and a Possible Link for Disease Predisposition. J Clin Invest 1979; 64:938.

    Article  PubMed  CAS  Google Scholar 

  7. Lopez de Castro JA, Barbosa JA, Krangel MS, Biro PA and Strominger JL: Structural Analysis of the Functional Sites of Class I HLA Antigens. Immunol Revs 1985; 85:149–168.

    Article  CAS  Google Scholar 

  8. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC: Structure of the Human Class I Histocompatibility Antigen HLA-A2. Nature 1987; 329:506–612.

    Article  PubMed  CAS  Google Scholar 

  9. Lawlor DA, Zemmour J, Ennis PD and Parham P: Evolution of Class I MHC Genes and Proteins: From Natural Selection to Thymic Selection. Ann Rev Immunol 1990; 8:23–63.

    Article  CAS  Google Scholar 

  10. Fuller AA, Trevithick JE, Rodey GE, Parham P and Fuller TC: Topographic Map of the HLA-A2 CREG Epitopes Using Human Alloantibody Probes. Human Immunol 1990; 28:284–305.

    Article  CAS  Google Scholar 

  11. Fuller AA, Rodey GE, Parham P and Fuller TC: Epitope Map of the HLA-B7 CREG Using Affinity-purified Human Alloantibody Probes. Human Immunol 1990; 28:306–325.

    Article  CAS  Google Scholar 

  12. Kormos RL, Colson YL, Hardesty RL Griffith BP, Trento A, Venkataramanan R, Duquesnoy RJ and Zeevi A: Immunologic and Blood Group Compatibility in Cardiac Transplantation. Transplant Proc 1988; 20(Suppl l):741–744.

    Google Scholar 

  13. Opelz G, Reichert B, Mollner H, et al: Preliminary Results of the Collaborative Heart Transplant Study. In Reichars, B (ed.): Recent Advances in Cardiovascular Surgery. Springer-Verlag, Heidelberg 1989.

    Google Scholar 

  14. Lavee J, Kormos RL, Duquesnoy RJ, Zerbe TR, Armitage JM, Vanek M, Hardesty RL and Griffith BP: Influence of Panel Reactive Antibody and Positive Lymphocytotoxic Crossmatch on Cardiac Transplant Survival. Int J Heart Transplantation (Submitted).

    Google Scholar 

  15. Brasile L, Zerbe T, Rabin B, Clarke J, Abrams A, Cerilli J: Identification of the Antibody to Vascular Endothelial Cells in Hyperacute Rejection in Patients Undergoing Cardiac Transplantation. Transplantation 1985; 40:672–674.

    Article  PubMed  CAS  Google Scholar 

  16. Braun WE: Laboratory and Clinical Management of the Highly Sensitized Organ Transplant Recipient. Human Immunol 1989; 26:245–250.

    Article  CAS  Google Scholar 

  17. Duquesnoy RJ: A Case of Hyperacute Rejection of a Cardiac Transplant. In: Terasaki P (ed): Visuals of the Clinical Histocompatibility Workshop. Los Angeles: One Lambda 1988; 6.

    Google Scholar 

  18. Demetris AJ, Jaffe R, Tzakis A, Ramsey G, Todo S, Belle S, Esquivel C, Shapiro R, Markus B, Mrozec E, Van Thiel DH, Sysyn G, Gordon R, Makowka L and Starzl TE: Antibody Mediated Rejection of Human Orthotopic Liver Allografts: A Study of Liver Transplantation Across ABO Blood Group Barriers. Am J Pathol 1988; 132:489–502.

    PubMed  CAS  Google Scholar 

  19. Iwatsuki S, Iwaki Y, Kano T, et al: Successful Liver Transplantation from Crossmatch Positive Donors. Transplant Proc 1981; 13:2876.

    Google Scholar 

  20. Fung JJ, Makowka L, Griffin M, Duquesnoy RJ, Tzakis A and Starzl TE: Successful Sequential Liver-kidney Transplantation in Patients With preformed Lymphocytotoxic Antibodies. Clin Transpl 1987; 1:187–194.

    Google Scholar 

  21. Margreiter R, Kornberger R, Koller J, et al: Transplant Proc 1987; 20:522.

    Google Scholar 

  22. Gubernatis G, Lauchart W, Jonker M, Steinhoff G, Bornscheuer A, Neuhaus P, Van Es AA, Kemnitz J, Wonigeit K, Pichlmayr R: Sings of Hyperacutre Rejection of Liver Grafts in Rhesus Monkeys after Donorspecific Presensitization. Transplant Proc 1987; 19:1082–1083.

    PubMed  CAS  Google Scholar 

  23. Knechtle SJ, Kolbeck PC, Tsuchimoto S, Coundouriotis A, Sanfilippo F, Bollinger RR: Humoral Rejection of rat Hepatic Transplants by Passive Transfer of Serum. Transplant Proc 1987; 19:1072–1076.

    PubMed  CAS  Google Scholar 

  24. Batts KP, Moore SB, Perkins JD, Weisner RH, Grambich PM and Krom RA: Influence of Positive Crossmatch and HLA Matching on Vanishing Bile Duct Syndrome in Human Liver Allografts. Transplantation 1988; 45:376.

    Article  PubMed  CAS  Google Scholar 

  25. Starzl TE, Demetris AJ, Todo S, Kang YG, Tzakis A, Duquesnoy R, Makowka L, Banner B, Concepcion W and Porter KA: Evidence of Hyperacute Rejection in Human Liver Grafts: The Case of Canary Kidneys. Clin. Transplant 1990; In press.

    Google Scholar 

  26. Daar AS, Fuggle SV, Fabre J, Ting A and Morris PJ: A Detailed Distribution of MHC Class II Antigens in Normal Human Organs. Transplantation 1984; 38:287.

    Article  PubMed  CAS  Google Scholar 

  27. Kamada N: The Immunology of Experimental Liver Transplantation in the Rat. Immunology 1985; 55:369.

    PubMed  CAS  Google Scholar 

  28. Demetris AJ, Markus B: Immunopathology of Liver Transplantation. CRC Crit Rev Immunol 1989; 9:67–92.

    CAS  Google Scholar 

  29. Wardle EN. Kuppfer Cells and their Function. Liver 1987; 7:63.

    PubMed  CAS  Google Scholar 

  30. Kakizoe S, Yanaga K, Starzl TE, Demetris AJ. Evaluation of Protocol Pre-transpplant and Post-reperfusion Biopsies from Human Orthotopic Liver Allografts: Considerations of “Preservation” and Early Immunologic Injury. Hepatology 1990; In press.

    Google Scholar 

  31. Gordon RJ, Fung JJ, Markus B, Fox I, Iwatsuki, Esquivel O, Tzakis A, Todo S and Starzl TE: The Antibody Crossmatch in Liver Transplantation. Surgery 1986; 100:705.

    PubMed  CAS  Google Scholar 

  32. Weber T, Marino IR, Kang YG, Esquivel CO, Starzl TE and Duquesnoy RJ: Intraoperative Blood Transfusions in Highly Alloimmunized Patients Undergoing Orthotopic Liver Transplantation. Transplantation 1989; 797–801.

    Google Scholar 

  33. Lewis JH, Bontempo FA, Cornell F, et al: Blood Use in Liver Transplantation. Transfusion 1987; 27:222.

    Article  PubMed  CAS  Google Scholar 

  34. Shaw BJ Jr, Martin DJ, Marquez JM, et al: Veno-venous By-pass in Clinical Liver Transplantation. Ann Surg 1984; 524.

    Google Scholar 

  35. Kang YG, Martin DJ, Marquez J, et al: Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation. Anesth Analg 1985; 64:888.

    Article  PubMed  CAS  Google Scholar 

  36. Kang YG, Lewis JH, Navalgund A, et al: Epsilon-aminocapzoic Acid for Treatment for Fibrinolysis During Liver Transplantation. Anesthesiology 1987; 66:766.

    Article  PubMed  CAS  Google Scholar 

  37. Terasaki PI, Marehioro TL, Starzl TE: Histocompatibility Testing. Washington, DC: National Acad Science National Research Council 1965; 83.

    Google Scholar 

  38. Kissmeyer-Nielsen F, Olsen S, Peterson VP, et al: Lancet 1966; 2:662.

    Article  PubMed  CAS  Google Scholar 

  39. Gore SM and Bradley BA: Renal Transplantation: Sense and Sensitization (Kluwer Academic Publishers Group, Dordrecht, The Netherlands 1988; 268.

    Google Scholar 

  40. Claas FJH, van Leeuwen A, van Rood JJ: Hyperimmunized Patients Do Not Need to Wait for an HLA Identical Donor. Tissue Antigens 1989; 34:23.

    Article  PubMed  CAS  Google Scholar 

  41. Oldfather JW, Anderson CB, Phelan DB, Cross DE, Luger AM and Rodey GE: Prediction of Crossmatch Outcome in Highly Sensitized Dialysis Patients Based On the Identification of Serum HLA Antibodies. Transplantation 1986; 43:267.

    Article  Google Scholar 

  42. Delmonico FL, Fuller A, Cosimi AB, Tolkoff-Rubin N, Russell PS, Rodey GE and Fuller TC: New Approaches to Donor Crossmatching and Successful Transplantation of Highly Sensitized Patients. Transplantation 1983; 36:629.

    Article  PubMed  CAS  Google Scholar 

  43. Van Eijck ELCL, van der Keur C, Gijbels Y, Bruning JW, van Rood JJ, Claas FJH: A Microabsorption Assay to Determine Acceptable HLA-A and B Mismatches for Highly Immunized Patients. Transpl Proc 1989; 21:724.

    Google Scholar 

  44. Oldfather JW, Phelam DL and Rodey GE: Preselection of Donors Based On the Identification of HLA Antibodies in Multiple Transferred Hematology Patients. Blood 1984; 64:229.

    Google Scholar 

  45. LeFor WM, Gilman NT, Niblack GD and Sanfilippo FL Use of SEOPF Regional Crossmatch Trays to Share Kidneys for Sensitized Patients. Transplantation 1985; 40:637.

    Article  PubMed  CAS  Google Scholar 

  46. Schafer AJ, Hasert K and Opelz G: Collaborative Transplant Study Crossmatch and Antibody Project. Transpl Proc 1985; 17:2469.

    Google Scholar 

  47. Duquesnoy RJ, White L, Fierst J, Vanek M, Banner B, Iwaki Y, and Starzl TE: Multiscreen Analysis of Highly Sensitized Renal Dialysis Patients for Antibodies Towards Public and Private Class I HLA Determinants: Implications for Computer-predicted Acceptable and Unacceptable Donor Mismatches in Kidney Transplantation. Transplantation 1990; In press.

    Google Scholar 

  48. Kennedy LJ, Marsh SGE and Bodmer J: Cytotoxic Monoclonal Antibodies. In Dupont B (Edit) Immunobiology of HLA. Vol. 1. Histocompatibility Testing (Springer-Verlag, NY) 1987; 301.

    Google Scholar 

  49. Iwaki Y, Lau M, Terasaki PI: Successful Transplants Across T Warm-positive Crossmatched due to IgM Antibodies. Clin Transpl 1988; 2:81.

    Google Scholar 

  50. Kreisler JM, Rementeria MC, DePablo R and Moreno ME: HLA-DR2, A Marker for Class I Antigen Sensitization. Transplantation 1986; 45:1071.

    Article  Google Scholar 

  51. Lohrmann HP, Bull MI, Decter JA, Yanka RA and Graw RG: Platelet Transfusions from HLA-coinpatible Unrelated Donors to Alloimmunized Patients. Ann Intern Med 1974; 80:9–15.

    PubMed  CAS  Google Scholar 

  52. Duquesnoy RJ, Filip DJ and Aster RH: Influence of HLA-A2 on the Effectiveness of Platelet Transfusions in Alloimmunized Thrombocytopenic Patients. Blood 1977; 50:407–412.

    PubMed  Google Scholar 

  53. Duquesnoy RJ: Donor Selection in Platelet Transfusion Therapy of Alloimmunized Thrombocytopenic Patients. In The Blood Platelet in Transfusion Therapy, edited by G.A. Jamieson and T. Greenwalt (Alan R. Liss, Inc., New York), 1978; 229–243.

    Google Scholar 

  54. Duquesnoy RJ, Filip DJ, Rimm AA, Rodey GE and Aster RH: Successful Transfusion of Platelets “Mismatched” for HLA Antigens to Alloimmunized Thrombocytopenic Patients. Am. J. Hematol 1977; 2:219–226.

    Article  PubMed  CAS  Google Scholar 

  55. Duquesnoy RJ, Testin J, Aster RH: Variable Expression of w4 and w6 on Platelets: Possible Relevance to Platelet Transfusion Therapy of Alloimmunized Thrombocytopenic Patients. Transplant Proc 1977; 9:1829–31.

    PubMed  CAS  Google Scholar 

  56. McElligott MN, Menitove JE, Duquesnoy RJ, Hunter JB and Aster RH: Effect of HLA Bw4/Bw6 Compatibility on Platelet Transfusion Response of Refractor Thrombocytopenic Patients. Blood 1982; 59:971–74.

    PubMed  CAS  Google Scholar 

  57. Liebert M and Aster RH: Expression of HLA-B12 on Platelets, on Lymphocytes and in Serum: A Quantitative Study. Tissue Antigens 1977; 9:199–208.

    Article  PubMed  CAS  Google Scholar 

  58. Szatkowski N, Duquesnoy RJ and Aster Rh: Further Studies of the Expression of Bw4, Bw6 and Other Antigens on the HLA-B Locus on Human Platelets. Transpl Proc 1978; 10:739–740.

    CAS  Google Scholar 

  59. Lalezari P and Driscoll AM: Ability of Thrombocytes to Acquire HLA Specificity from Plasma. Blood 1982; 59:167–70.

    PubMed  CAS  Google Scholar 

  60. Blumberg N, Masel D, Mayer T, Horan P and Heal J: Removal of HLA-A,B Antigens from Platelets. Blood 1976; 63:448–50.

    Google Scholar 

  61. Kao KJ: Selective Elution of HLA Antigens and Beta-2-Microglobulin from Human Platelets by Chloroquine Diphosphate. Transfusion 1988; 28:14–17.

    Article  PubMed  CAS  Google Scholar 

  62. Kao KJ, Scornile JC, Riley WJ and McQueen CF: Association Between HLA Phenotype and HLA Concentration in Plasma or Platelets. Human Immunol 1988; 21:115–124.

    Article  CAS  Google Scholar 

  63. Saidman S, Marrari M, Kiss JE and Duquesnoy RJ: Expression of Public and Private Epitopes of the B7 CREG on Platelets and Lymphocytes (In preparation).

    Google Scholar 

  64. Duquesnoy RJ, Filip DJ, Tomasulo PA and Aster RH: Role of HLA-C Matching in Histocompatible Platelet Transfusion Therapy of Alloimmunized Thrombocytopenic Patients. Transpl. Proc. 1977; 9:1827–1829.

    CAS  Google Scholar 

  65. Duquesnoy RJ, Anderson AJ, Tomasulo PA and Aster RH: ABO Compatibility and Platelet Transfusions of Alloimmunized Thrombocytopenic Patients. Blood 1979; 54:595–599.

    Google Scholar 

  66. Heal JM, Blumberg N and Masel D: An Evaluation of Crossmatching, HLA, and ABO Matching for Platelet Transfusions to Refractory Patients. Blood 1987; 70:23–30.

    PubMed  CAS  Google Scholar 

  67. Filip DJ, Duquesnoy RJ and Aster RH: Predictive Value of Crossmatching for Transfusion of Platelet Concentrates to Alloimmunized Recipients. Am J Hematol 1976; 1:471–479.

    Article  PubMed  CAS  Google Scholar 

  68. Kakaiya RM, Gudino MD, Miller WV, et al: Four Crossmatch Methods to Select Platelet Donors. Transfusion 1984; 24:35.

    Article  PubMed  CAS  Google Scholar 

  69. McFarland JG, Aster RH: Evaluation of Four Methods for Platelet Compatibility Testing. Blood 1987; 69:1425.

    PubMed  CAS  Google Scholar 

  70. Brand A, van Leeuwen A, Eernisse JG, van Rood JJ: Platelet Transfusion Therapy. Optimal Donor Selection with a Combination of Lymphocytotoxicity and Platelet Fluorescence Tests. Blood 1987; 51:1781.

    Google Scholar 

  71. Freedman J, Garvey MB, Salomon de Friedberg Z, Hornstein A, and Blanchette V: Random Donor Platelet Crossmatching: Comparison of Four Platelet Antibody Detection Methods. Am J Hematol 1988; 28:1–7.

    Article  PubMed  CAS  Google Scholar 

  72. Kickler TS, Ness PM and Braine HG: Platelet Crossmatching. A Direct Approach to the Selection of Platelet Transfusions for the Alloimmunized Thrombocytopenic Patient. Am J Clin Pathol 1988; 90:69–76.

    PubMed  CAS  Google Scholar 

  73. Welch HG, Larson EB and Schlichter SJ: Providing Platelets to Refractory Patients. Prudent Strategies (Editorial). Transfusion 1989; 29:193–195.

    Article  PubMed  CAS  Google Scholar 

  74. Macpherson BR, Hammond PB and Maniscalco CA: Alloimmunization to Public HLA Antigens Mn multi-transfused Platelet Recipients. Ann Clin Lab Sci 1986; 16:38–44.

    PubMed  CAS  Google Scholar 

  75. Brubaker DB and Romine M: Relationship of HLA and Platelet-reactive Antibodies in Alloimmunized Patients Refractory to Platelet Therapy. Am J of Hematol 1987; 26:341–352.

    Article  CAS  Google Scholar 

  76. Taube DH, Williams DG, Cameron JS et al: Renal Transplantation After Removal and Prevention of Resynthesis of HLA Antibodies. Lancet 1984; 1:824–828.

    Article  PubMed  CAS  Google Scholar 

  77. Palmer A, Taube D, Welsh K, Brynger H, Delin K, Gjorstrop P, Konar J and Soderstrom T: Extracorporal Immunoadsorption of Anti-HLA Antibodies: Preliminary Clin Experience. Transplant Proc 1987; 19:3750–3751.

    PubMed  CAS  Google Scholar 

  78. Reed E, Hardy M, Benvenisty A, Lattes C, Brensilver J, McCabe R, Reemtsma K, King DQ and Suciu-Foca N: Effect of Anti-idiotypic Antibodies to HLA on Graft Survival in Renal Allograft Recipients. N Eng J Med 1987; 316:1450–1453.

    Article  CAS  Google Scholar 

  79. Zeigler ZR, Shadduck RK, Rosenfield CS, Mangan KF, Winkelstein A, Oral A, Ramsey GE and Duquesnoy RJ: High Dose Intravenous Gammaglobulin Improves Responses to Single-donor Platelets in Patients Refractory to Platelet Transfusion. Blood 1987; 70:1433–1436.

    PubMed  CAS  Google Scholar 

  80. Slichter SJ: Prevention of Platelet Alloimmunization. In Muraski K. (ed.) Transfusion Medicine: Recent Technological Advances, New York, Alan R. Liss 1985; 83–116.

    Google Scholar 

  81. Brand A, Claas FHJ, Voogt PJ, Wasser MNJM and Eernisse JG: Alloimmunization after Leukocyte-depleted Multiple Random Donor Platelet Transfusions. Am J Clin Pathol 1988; 90:69–76.

    Google Scholar 

  82. Kahn RA, Duffy BF and Rodey GE: Ultraviolet Irradiation of Platelet Concentrat Abrogates Lymphocyte Activation Without Affecting Platelet Function in Vitro. Transfusion; 25:547–550.

    Google Scholar 

  83. Deeg HJ: Transfusions With a Tan: Prevention of Allosensitization by Ultraviolet Irradiation. Transfusion 1989; 29:449–455.

    Article  Google Scholar 

  84. Murphy MF, Metcalf P, Thomas H, Eve J, Ord J, Lister TA and Waters AH: Use of Leukocyte-poor Blood Components and HLA-matched Platelet Donors to Prevent HLA Alloimmunization. Br J Haematol 1986; 62:529–535.

    Article  PubMed  CAS  Google Scholar 

  85. Lagaay EL, Hennemann IP, Ruigrok IP, deHaan MW, Persyn GG, Termijtelen A, Hendricks GF, Weimar W, Claas FH, VanRood JJ: Effect of One HLA-DR Antigen-matched and Completely HLA-DR Mismatched Blood Transfusions on Survival of Heart and Kidney Allograft. N Engl J Med 1989; 321:701–705.

    Article  Google Scholar 

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  1. René J. Duquesnoy
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Editors and Affiliations

  1. Biomedical Research and Development The Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland, 20855, USA

    John Lee

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Duquesnoy, R.J. (1990). HLA Humoral Allosensitization. In: Lee, J. (eds) The HLA System. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-3454-8_2

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  • DOI: https://doi.org/10.1007/978-1-4612-3454-8_2

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