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Thromb Haemost 1995; 74(06): 1557-1563
DOI: 10.1055/s-0038-1649982
Original Articles
Platelets
Schattauer GmbH Stuttgart

Role of FCγRIIA Gene Polymorphism in Human Platelet Activation by Monoclonal Antibodies

Christilla Bachelot
INSERM 428, Faculté des Sciences Pharmaceutlques, Paris, France
,
Raphaël Saffroy
INSERM 428, Faculté des Sciences Pharmaceutlques, Paris, France
,
Sophie Gandrille
INSERM 428, Faculté des Sciences Pharmaceutlques, Paris, France
,
Martine Aiach
INSERM 428, Faculté des Sciences Pharmaceutlques, Paris, France
,
Francine Rendu
INSERM 428, Faculté des Sciences Pharmaceutlques, Paris, France
› Author Affiliations
Further Information

Publication History

Received 04 April 1995

Accepted after resubmission 18 August 1995

Publication Date:
10 July 2018 (online)

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Summary

The aim of this study was to determine if there is a correlation between the activity of a MoAb as an agonist and its ability to bind to the Fc platelet receptor, FcγRIIa. A polymorphism at amino acid 131 [arginine (Arg) or histidine (His)] of FcγRIIa was first shown to be determinant for MoAb-IgG1 binding on monocytes. To clarify the role of this polymorphism in platelet activation by MoAb-IgG1 we (i) established the FCγRIIA polymorphism at the gene level by adapting the denaturating gradient gel electrophoresis method, (ii) analyzed the binding affinity of the MoAbs to FrγRIIa on platelets from homozygous Arg, homozygous His, and heterozygous Arg/His donors, and (iii) characterized the different reactivities of platelets according to the FCγRIIA polymorphism. Among 167 Caucasian donors we found 46% heterozygous Arg/His, 36% homozygous His and 18% homozygous Arg. ALB6, an anti CD9, P256 an anti GPIIb-IIIa, and AP3 an anti-GPIIIa were chosen according to their ability (ALB6, P256) or not (AP3) to activate platelets. These 3 MoAbs-IgG1 bind to FcγRIIa with a stronger affinity for the Arg-form of FcγRIIa, a result which was confirmed with the use of diverse MoAbs directed against various antigens. The different abilities of MoAbs to bind to the two FcγRIIa forms were well correlated to the different platelet responses induced by ALB6 and P256. However, low concentrations of ALB6, which allow full activation of platelets from homozygous Arg donors, as did P256, did not induce any activation of platelets from homozygous His donors, whereas P256 is able to induce a low aggregation. The results further define the respective roles of the antigen and the Fc receptor, depending on the MoAb, and the role of the FcγRIIa polymorphism in platelet activation induced by MoAbs. In addition, the results obtained with MoAbs unable to induce platelet activation provide evidence that the binding of a MoAb on FcγRIIa does not predict its ability to activate platelets.

 

  • References

  • 1 von dem Borne AE G Kr, Modderman PW, Admiraal LG, Nieuwenhuis HK. Platelet antibodies, the overall results. In: Leukocyte typing IV. Knapp W, Dörken B, Gilks WR, Rieber EP, Schmidt RE, Stein H, von dem Borne AE G Kr. eds Oxford University Press; 1989. pp 951-966
    Google Scholar
  • 2 Pidard D, Montgomery RR, Bennett JS, Kunicki TJ. Interaction of AP2, a monoclonal antibody specific for human platelet glycoprotein IIb-IIIa complex, with intact platelets. J Biol Chem 1983; 258: 12582-12586
    PubMedGoogle Scholar
  • 3 Bennett JS, Hoxie JA, Leitman SF, Vilaire G, Cines DB. Inhibition of fibrinogen binding to stimulated platelets by a monoclonal antibody. Proc Natl AcadSci USA 1983; 80: 2417-2421
    CrossrefPubMedGoogle Scholar
  • 4 Scott JL, Dunn SM, Jin B, Hillam AJ, Walton S, Bemdt MC, Murray AW, Krissansen GW, Burns GF. Characterization of a novel membrane glycoprotein involved in platelet activation. J Biol Chem 1989; 264: 13475-13482
    PubMedGoogle Scholar
  • 5 Ockenhouse CF, Magowan C, Chulay JD. Activation of monocytes and platelets by monoclonal antibodies or malaria-infected erythrocytes binding to the CD36 surface receptor in vitro. J Clin Invest 1989; 84: 468-475
    CrossrefPubMedGoogle Scholar
  • 6 Anderson GP, van de Winkel JG J, Anderson CL L. Anti-GPIIb-IIIa (CD41) monoclonal antibody-induced platelet activation requires Fe receptor-dependent cell-cell interaction. Br J Haematol 1991; 79: 75-83
    CrossrefPubMedGoogle Scholar
  • 7 Morel MC, Lecompte T, Champeix P, Favier R, Potevin F, Samama M, Salmon C, Kaplan C. PL2-49, a monoclonal antibody against glycoprotein IIb which is a platelet activator. Br J Haematol 1989; 71: 57-63
    CrossrefPubMedGoogle Scholar
  • 8 De Reys S, Blom C, Lepoudre B, Declerck PJ, De Reys M, Vermylen J, Deckmyn H. Human platelet aggregation by murine monoclonal antiplatelet antibodies is subtype-dependent. Blood 1993; 81: 1792-1800
    PubMedGoogle Scholar
  • 9 Horsewood P, Hayward CP M, Warkentin TE, Kelton JG. Investigation of the mechanisms of monoclonal antibody-induced platelet activation. Blood 1991; 78: 1019-1021
    PubMedGoogle Scholar
  • 10 Rubinstein E, Urso I, Boucheix C, Carroll RC. Platelet activation by crosslinking HLA class I molecules and Fe receptor. Blood 1992; 79: 2901-2908
    PubMedGoogle Scholar
  • 11 Worthington RE, Carroll RC, Boucheix C. Platelet activation by CD9 monoclonal antibodies is mediated by the FeγRII receptor. Br J Haematol 1990; 74: 216-222
    CrossrefPubMedGoogle Scholar
  • 12 Slupsky JR, Cawley JC, Griffith LS, Shaw AR E, Zuzel M. Role of FeγRII in platelet activation by monoclonal antibodies. J Biol Chem 1992; 148: 3189-3194
    PubMedGoogle Scholar
  • 13 Bachelot C, Rendu F, Boucheix C, Hogg N, Levy-Toledano S. Activation of platelets induced by a mAb P256 specific for glycoprotein IIb-IIIa. Possible evidence for a role for IIb-IIIa in membrane signal transduction Eur J Biochem 1990; 190: 177-183
    CrossrefPubMedGoogle Scholar
  • 14 Bachelot C, Sulpice JC, Giraud F, Rendu F. Mechanisms involved in platelet activation induced by a monoclonal antibody anti glycoprotein IIb-IIIa: inositol phosphate production is not the primary event. Cell Signal 1991; 6: 537-546
    PubMedGoogle Scholar
  • 15 Modderman PW, Huisman HG, van Mourik JA, von dem Borne AE G Kr. A monoclonal antibody to the human platelet glycoprotein IIb/IIIa complex induces platelet activation. Thromb Haemost 1988; 60: 68-74
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 De Reys S, Hoylaerts MF, De Ley M, Vermylen J, Deekmyn H. Fe-independent cross-linking of a novel platelet membrane protein by a monoclonal antibody causes platelet activation. Blood 1994; 84: 547-555
    PubMedGoogle Scholar
  • 17 Frelinger III AL, Du X, Plow EF, Ginsberg MH. Monoclonal antibodies to ligand-occupied conformers of integrin αIIb-β1(glycoprotein IIb-IIIIa) alter receptor affinity, specificity, and function. J Biol Them 1991; 266: 17106-17111
    PubMedGoogle Scholar
  • 18 Thibert V, Cristofari M, Romagné O, Legrand C. Characterization of platelet panel CD36 mAb and a study of their effects on platelet activation. In: Leukocyte typing V. Schlossman SF, Boumsell L, Gilks W, Harlan JM, Kishimoto T, Morimoto C, Ritz J, Shaw S, Silverslein R, Springer T, Tedder TF, Todd RF. eds Oxford University Press; 1995. pp 1274-1278
    Google Scholar
  • 19 Berndt MC, Mazurov AV, Vinogradov DV, Burns GF, Chesterman CN. Topographical association of the platelet Fe-receptor with the glycoprotein IIb-IIIa complex. Platelets 1993; 4: 190-196
    CrossrefPubMedGoogle Scholar
  • 20 Ravetch JV. Fe receptors: rubor redux. Cell 1994; 78: 553-560
    CrossrefPubMedGoogle Scholar
  • 21 van de Winkel JG J, Capel PJ A. Human IgG Fe receptor heterogeneity: molecular aspects and clinical implications. Immunol Today 1993; 14: 215-221
    CrossrefPubMedGoogle Scholar
  • 22 Stuart wS G, Simister NE, Clarkson SB, Kaeinski BM, Shapiro M, Mellman I. Human IgG Fe receptor (hFeRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium. EMBO J 1989; 8: 3657-3666
    PubMedGoogle Scholar
  • 23 Brooks DG, Qiu WQ, Luster AD, Ravetch JV. Structure and expression of human IgG FeRII(CD32). J Exp Med 1989; 170: 1369-1385
    CrossrefPubMedGoogle Scholar
  • 24 Hibbs ML, Bonadonna L, Scott BM, McKenzie IF C, Hogarth PM. Molecular cloning of a human immunoglobulin G Fe receptor. Proc Natl Acad Sci USA 1988; 85: 2240-2244
    CrossrefPubMedGoogle Scholar
  • 25 Stengelin S, Stamenkovic I, Seed B. Isolation of cDNAs for two distinct human Fe receptors by ligand affinity cloning. EMBO J 1988; 7: 1053-1059
    PubMedGoogle Scholar
  • 26 Qiu WQ, de Bruin D, Brownstein BH, Pearse R, Ravetch JV. Organization of the human and mouse low-affinity FeγR genes: Duplication and recombination. Science 1990; 248: 732-735
    CrossrefPubMedGoogle Scholar
  • 27 Tax WJ M, Hermes FF M, Willems RW, Capel PJ A, Koene RA P. Fe receptors for mouse IgGl on human monocytes: polymorphism and role in antibody- induced T cell proliferation. J Immunol 1984; 133: 1185-1189
    PubMedGoogle Scholar
  • 28 Clark MR, Clarkson SB, Ory PA, Stollman N, Goldstein IM. Molecular basis for a polymorphism involving Fe receptor II on human monocytes. J Immunol 1989; 143: 1731-1734
    PubMedGoogle Scholar
  • 29 Warmerdam PA M, van de Winkel JG J, Gosselin EJ, Capel PJ A. Molecular basis for a polymorphism of human Feγ receptor II (CD32). J Exp Med 1990; 172: 19-25
    CrossrefPubMedGoogle Scholar
  • 30 Warmerdam PA M, Parren PW H I, Vlug A, Aarden LA, van de Winkel JG J, Capel PJ A. Polymorphism of the human Feγ Receptor II (CD32): Molecular basis and functional aspects. Immunobiol 1992; 185: 175-182
    CrossrefPubMedGoogle Scholar
  • 31 Gosselin EJ, Brown MF, Anderson CL, Zipf TF, Guyre PM. The monoclonal antibody 41H16 detects the Leu 4 responder form of human FeγRII. J Immunol 1990; 144: 1817-1822
    PubMedGoogle Scholar
  • 32 Anderson CL, Ryan DH, Looney RJ, Leary PC. Structural polymorphism of the human monocyte 40 kilodalton Fe receptor for IgG. J Immunol 1987; 138: 2254-2256
    PubMedGoogle Scholar
  • 33 Cassel DL, Keller MA, Surrey S, Schwartz E, Schreiber AD, Rapaport EF, McKenzie SE. Differential expression of FeγRIIA, FeγRIIB and FeγRIIC in hematopoietic cells. Analysis of transcripts Molec Immun 1993; 30: 451-460
    CrossrefPubMedGoogle Scholar
  • 34 Karas SP, Rosse WF, Kurlander RJ. Characterization of the IgG-Fe receptor on human platelets. Blood 1982; 60: 1277-1282
    PubMedGoogle Scholar
  • 35 Rosenfeld SI, Anderson CL. Fe receptors of human platelets. In: Platelet Immunobiology, Molecular and clinical aspects. Kunicki TJ, George JN. eds Lippincott Company; Philadelphia: 1989. pp 337-353
    Google Scholar
  • 36 King M, McDermott P, Schreiber AD. Characterization of the Feγ receptor on human platelets. Cell Immunol 1990; 128: 462-479
    CrossrefPubMedGoogle Scholar
  • 37 Looney RJ, Anderson CL, Ryan DH, Rosenfeld SI. Structural polymorphism of the human platelet Feγ receptor. J Immunol 1988; 141: 2680-2683
    PubMedGoogle Scholar
  • 38 Rosenfeld SI, Ryan DH, Looney RJ, Anderson CL, Abraham GN, Leddy JP. Human Feγ receptors: stable inter-donor variation in quantitative expression on platelets correlates with functional responses. J Immunol 1987; 138: 2869-2873
    PubMedGoogle Scholar
  • 39 Chong BH, Pilgrim RL, Cooley MA, Chesterman CN. Increased expression of platelet IgG Fe receptors in immune-induced thrombocytopenia. Blood 1993; 81: 988-993
    PubMedGoogle Scholar
  • 40 Tomiynma Y, Kunicki TJ, Zipf TF, Ford SB, Aster RH. Response of human platelets to activating monoclonal antibodies: Importance of FeγRII (CD32) phenotype and level of expression. Blood 1992; 80: 2261-2268
    PubMedGoogle Scholar
  • 41 Parren PW H I, Warmerdam PA M, Boeije LC M, Arts J, Westerdaal NA C, Vlug A, Capel PJ A, Aarden LA, van de Winkel JG J. On the interaction of the IgG subclasses with the low affinity FeγRIIa (CD32) on human monocytes, neutrophils, and platelets. J Clin Invest 1992; 90: 1537-1546
    CrossrefPubMedGoogle Scholar
  • 42 Boueheix C, Soria C, Mirshahi M, Soria J, Perrot JY, Fournier N, Billard M, Rosenfeld C. Characteristics of platelet aggregation induced by the monoclonal antibody ALB6 (acute lymphoblastic leukemia antigen p24). FEBS lett 1983; 161: 289-295
    CrossrefPubMedGoogle Scholar
  • 43 Bai Y, Durbin II, Hogg N. Monoclonal antibodies specific for platelet glycoproteins react with human monocytes. Blood 1984; 64: 139-146
    PubMedGoogle Scholar
  • 44 Newman PJ, Allen RW, Kahn RA, Kunicki TJ. Quantitation of membrane glycoprotein IIIa on intact human platelets using the monoclonal antibody, AP3. Blood 1985; 65: 227-232
    PubMedGoogle Scholar
  • 45 Looney RJ, Abraham GN, Anderson CL. Human monocytes and U937 cells bear two distinct F’c receptors for IgG. J Immunol 1986; 136: 1641-1647
    PubMedGoogle Scholar
  • 46 Bell G, Karam J, Rutter W. Polymorphic DNA region adjacent to the 5’ end of the human insulin gene. Proc Natl Acad Sci USA 1981; 78: 5759-5763
    CrossrefPubMedGoogle Scholar
  • 47 Lerman LS, Silverslein K. Computational simulation of DNA melting and its application to denaturing gradient gel electrophoresis. Methods Enzymol 1987; 155: 482-501
    PubMedGoogle Scholar
  • 48 Newton CR, Graham A, Heptinstall LE, Powell SJ, Summers C, Kalsheker N, Smith JC, Markham AF. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS) Nucl Acids Res 1989; 17: 2503-2516
    CrossrefPubMedGoogle Scholar
  • 49 Attree O, Vidaud D, Vidaud M, Amselem S, Lavergne JM, Goossens M. Mutations in the catalytic domain of human coagulation factor IX: rapid characterization by direct genomic sequencing of DNA fragments displaying an altered melting behavior. Genomics 1989; 4: 266-272
    CrossrefPubMedGoogle Scholar
  • 50 Gyllensten UB, Erlich HA. Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLKA-DQA locus. 1988; 85: 7652-7656
    PubMedGoogle Scholar
  • 51 Newman PJ, McEver RP, Doers MP, Kunicki TJ. Synergistic action of two murine monoclonal antibodies that inhibit ADP-induced platelet aggregation without blocking fibrinogen binding. Blood 1987; 69: 668-676
    PubMedGoogle Scholar
  • 52 Abo T, Tilden AB, Balch CM, Kumagai K, Troup GM, Cooper MD. Ethnic differences in the lymphocyte proliferative response induced by a murine IgGl antibody, Leu-4, to the T3 molecule. J Exp Med 1984; 160: 303-309
    CrossrefPubMedGoogle Scholar
  • 53 Clark MR, Stuart SG, Kimberly RP, Ory PA, Goldstein IM. A single amino acid distinguishes the high-responder from the low-responder form of Fe receptor II on human monocytes. Eur J Immunol 1991; 21: 1911-1916
    CrossrefPubMedGoogle Scholar
  • 54 Reilly AF, Norris CF, Surrey S, Bruchak FJ, Rapaport EF, Schwartz E, McKenzie SE. Genetic diversity in human Fe receptor II for immunoglobulin G: Feγ Receptor IIA ligand-binding polymorphism. 1994; 1: 640-644
    PubMedGoogle Scholar
  • 55 Isenhart CE, Ahmed A, Anderson CL, Brandt JT. The response of donor platelets to heparin-induced thrombocytopenia is dependent on platelet FeγRII phenotype. Thromb Haemost 1993; 69: 2321a (abstr)
    PubMedGoogle Scholar
  • 56 Osborne JM, Chacko GW, Brandt JT, Anderson CL. Ethnic variation in frequency of an allelic polymorphism of human FeγRIIA determined with allele specific oligonucleotide probes. J Immunol Meth 1994; 173: 207-217
    CrossrefPubMedGoogle Scholar
  • 57 Bachelot C, Cano E, Grelac F, Saleun S, Druker BJ, Levy-Toledano S, Fischer S, Rendu F. Functional implications of tyrosine protein phosphorylation in platelets. Biochem J 1992; 284: 923-928
    CrossrefPubMedGoogle Scholar
  • 58 MacIntyre EA, Roberts PJ, Jones M, van der Schoot CE, Favalaro EJ, Tidman N, Linch D. Activation of human monocytes occurs on cross-linking monocytic antigens to an Fe receptor. J Immunol 1989; 142: 2377-2383
    PubMedGoogle Scholar
  • 59 Jennings LK, Crossno JT, Fox CF, White MM, Green CA. Platelet p24/CD9, a member of the tetraspanin family of proteins. Platelet-dependent vascular occlusion Annals New York Acad Science 1994; 714: 175-184
    PubMedGoogle Scholar
  • 60 Lund J, Takahashi N, Pound JD, Goodall M, Nakagawa H, Jefferis R. Oligosaccharide-protein interactions in IgG can modulate recognition by Feγ receptors. FASEB 1995; 9: 115-119
    CrossrefPubMedGoogle Scholar
  • 61 Kunicki TJ, Newman PJ. The molecular immunology of human platelet proteins. Blood 1992; 80: 1386-1404
    PubMedGoogle Scholar