RSS-Feed abonnieren
DOI: 10.1055/s-0038-1661555
A Two-Site, Monoclonal Antibody-Based Immunoassay for von Willebrand Factor -Demonstration that vWF Function Resides in a Conformational Epitope
Publikationsverlauf
Received 21. Januar 1986
Accepted after revision 06. März 1986
Publikationsdatum:
26. Juli 2018 (online)
Summary
Two monoclonal antibodies (RFF-VIII: R/l and RFF-VIII:R/ 2) which recognise the same epitope on von Willebrand factor (vWF) have been used in a simple, two-site, solid-phase immunoradiometric (IRMA) or enzyme-linked assay (ELISA) to analyse vWF in plasma from normal individuals and from patients with von Willebrand’s disease (vWD). Results obtained confirm our previous findings (using RFF-VIII :R/2 in a one-site, fluid-phase IRMA) that the MAbs detect the presence of an epitope on the vWF molecule that reflects its function. This epitope is involved in vWF binding to the GPIb protein on platelets. It is reduced in all types of vWD, including type II (or variant) vWD. It is present in normal plasma, in vWF released from normal platelets and from cultured umbilical cord vein endothelial cells. The epitope is, however, found to be reduced in serum. Studies on SDS-treated vWF prove that this GPIb-binding site is dependent on the conformation of the vWF multimers.
-
References
- 1 Jaffe EA, Hoyer LW, Nachman RL. Synthesis of von Willebrand factor by human endothelial cells. Proc Natl Acad Sci USA 1974; 71: 1906-1909
- 2 Howard MA, Montgomery DC, Hardisty RM. Factor VUI-related antigen in platelets. Thromb Res 1974; 4: 617-624
- 3 Nachman RL, Levine R, Jaffe EA. Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes. J Clin Invest 1977; 60: 914-921
- 4 Doucet-de Bruine MH, Sixma JJ, Over J, Beeser-Visser NH. Heterogeneity of human factor VIII. II. Characterization of forms of factor VIII binding to platelets in the presence of ristocetin. J Lab Clin Med 1978; 92: 96-107
- 5 Counts RB, Paskell SL, Elgee SK. Disulfide bonds and the quaternary structure of factor VIII/von Willebrand factor. J Clin Invest 1978; 62: 702-709
- 6 Gralnick HR, Williams SB, Morisato DK. Effect of the multimeric structure of the factor VIII/von Willebrand factor protein on binding to platelets. Blood 1981; 58: 387-397
- 7 Sixma JJ, Sakariassen KS, Beeser-Visser NH, Ottenhof-Rovers M, Bolhuis PA. Adhesion of platelets to human artery subendothelium: effect of factor VIII/von Willebrand factor of various multimeric composition. Blood 1984; 63: 128-139
- 8 Gralnick HR, Coller BS. Platelets stimulated with thrombin and ADP bind von Willebrand factor to different sites than platelets stimulated with ristocetin. Clin Res 1983; 3: 482a
- 9 Ruggeri ZM, De Marco L, Gatti L, Bader R, Montgomery RR. Platelets have more than one binding site for von Willebrand Factor. J Clin Invest 1983; 72: 1-12
- 10 Nokes T JC, Mahmoud NA, Savidge GF, Goodall AH, Meyer D, Edgington TS, Hardisty RM. Von Willebrand factor has more than one binding site for platelets. Thromb Res 1984; 34: 361-366
- 11 Sakariassen KS, Bolhuis PA, Sixma JJ. Human blood platelet adhesion to artery subendothelium is mediated by factor VIII von Willebrand factor bound to the subendothelium. Nature 1979; 279: 636-637
- 12 Sixma JJ, Sakariassen KS, Stel HV, Houdijk W PM, In der Maur DW, Hamer RJ, de Groot PG, Van Mourik JA. Functional domains on von Willebrand factor. Recognition of discrete tryptic fragments by monoclonal antibodies that inhibit interaction of von Willebrand factor with platelets and with collagen. J Clin Invest 1984; 74: 736-744
- 13 Kao KJ, Pizzo SV, McKee PA. Demonstration and characterization of specific binding sites for factor VIII/von Willebrand factor on human platelets. J Clin Invest 1979; 63: 656-664
- 14 Morisato DK, Gralnick HR. Selective binding of the factor VIII/von Willebrand factor protein to human platelets. Blood 1980; 55: 9-15
- 15 Girma JP, Kalafatis M, Pietu G, Lavergne JM, Edgington TS, Meyer D. Mapping of functional domains of human von Willebrand factor using monoclonal antibodies. Thromb Haemostas 1985; 54: 59 (Abstr)
- 16 Fretto LJ, Fowler WE, Hamilton KK, McKee PA. Substructure of human von Willebrand factor (vWF) protomer: fragmentation by plasmin and S. aureus V8 protease. Thromb Haemostas 1985; 54: 59 (Abstr)
- 17 Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease. Characterization of two subtypes by analysis of multimeric composition of factor VUI/von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65: 1318-25
- 18 Meyer D, Obert B, Pietu G, Lavergne JM, Zimmerman TS. Multimeric structure of factor VIII/von Willebrand factor in von Willebrand’s disease. J Lab Clin Med 1980; 95: 590-602
- 19 Ruggeri ZM, Pareti FI, Mannucci PM, Ciavarella N, Zimmerman TS. Heightened interaction between platelets and factor VIII/ von Willebrand factor in a new subtype of von Willebrand’s disease. N Engl J Med 1980; 302: 1047-1051
- 20 Hoyer LW, Rizza CR, Tuddenham E GD, Carta CA, Armitage H, Rotblat F. The VIIIR:Ag multimer patterns in von Willebrand’s disease. Br J Haematol 1983; 55: 493-507
- 21 Tuddenham E GD. The varieties of von Willebrand’s disease. Clin Lab Haemat 1984; 6: 307-323
- 22 Goodall AH, Jarvis J, Chand S, Rawlings E, O’Brien DP, McGraw A, Hutton R, Tuddenham E GD. An immunoradiometric assay for human Factor VII I/von Willebrand Factor (VIII: vWF) using monoclonal antibodies that define a functional epitope. Brit J Haematol 1985; 59: 565-577
- 23 McCraw A, Tuddenham E GD, Goodall AH. Monoclonal antibody-based IRMA for vWD: Patient Survey. Thromb Haemostas 1985; 54: 171 (Abstr)
- 24 Ey PL, Prowse SJ, Jenkin CR. Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry 1978; 15: 429-436
- 25 Avrameas S. Coupling of enzymes to proteins with glutaraldehyde. Use of the conjugates for the detection of antigens and antibodies. Immunochemistry 1969; 6: 43-52
- 26 Hoyer LW. Immunologic studies of anti-hemophilic factor (AHF, factor VIII) IV: Radioimmunoassay for AHF antigen. J Lab Clin Med 1972; 80: 822-833
- 27 Zimmerman TS, Hoyer LW, Dickson L, Edgington TS. Determination of the von Willebrand’s disease antigen (factor VIII-related antigen) in plasma by quantitative immunoelectrophoresis. J Lab Clin Med 1975; 86: 152-159
- 28 Kirkwood T BL, Barrowcliffe TW. Standardization of factor VIII. II. A British standard for factor VIII related antigen. Br J Haematol 1980; 46: 483-490
- 29 Weiss HJ, Hoyer LW, Rickies FR, Varma A, Rogers J. Quantitative assay of a plasma factor deficient in von Willebrand’s disease that is necessary for platelet aggregation. J Clin Invest 1973; 52: 2708-16
- 30 Hutton RA, Howard MA, Deykin D, Hardisty RM. Methods for the separation of platelets from plasma. Thromb Diathes Haemorrh 1974; 31: 119-133
- 31 Lloyd UV, Tunbridge LJ, Rogers SE, Hondow JA, Russell WJ. Destruction of ristocetin cofactor by coagulation at 4° C. Thromb Res 1985; 37: 659-668
- 32 Koutts J, Walsh PN, Plow EF, Fenton JW, Bouma BN. Active release of human platelet factor VUI-related antigen by adenosine diphosphate, collagen, and thrombin. J Clin Invest 1978; 62: 1255-1263
- 33 Fernandez M FL, Ginsberg MH, Ruggeri ZM, Battle FJ, Zimmerman TS. Multimeric structure of platelet factor VIII/von Willebrand factor: The presence of larger multimers and their reassociation with thrombin-stimulated platelets. Blood 1982; 60: 1132-1138
- 34 Wagner DD, Marder VJ. Biosynthesis of von Willebrand protein by human endothelial cells. J Biol Chem 1983; 258: 2065-2067
- 35 Levine JD, Harlan JM, Harker LA, Joseph ML, Counts RB. Thrombin-mediated release of factor VIII antigen from human umbilical vein endothelial cells in culture. Blood 1982; 60: 531-534
- 36 Goodall AH, Jarvis J, Bofill M, Hunter N, MacGreggor I, Tuddenham E GD. Antigenic variation in VIII :RAg in platelets defined by a monoclonal antibody to a functional site. Thromb Haemostas 1983; 50: 308 (Abstr)
- 37 Jeanneau C, Avner P, Sultan Y. Use of monoclonal antibody and colloidal gold in E. M. localization of von Willebrand factor in megakaryocytes and platelets. Cell Biol Int Rep 1984; 8: 841-8
- 38 Cramer EM, Meyer D, le Menn R, Breton-Gorius J. Eccentric localization of von Willebrand factor in an internal structure of platelet α-granule resembling that of Weibel-Palade bodies. Blood 1985; 66: 710-713
- 39 Hormia M, Lehto VP, Vitanen I. Intracellular localization of factor VIII-related antigen and fibronectin in cultured human endothelial cells: evidence for divergent routes of intracellular translocation. Eur J Cell Biol 1984; 33: 217-228
- 40 Stel HV, Sakariassen KS, Scholte BJ, Veerman E CI, van der Kwast TH, de Groot PG, Sixma JJ, van Mourik JA. Characterization of 25 monoclonal antibodies to factor VIII von Willebrand factor: Relationship between ristocetin-induced platelet aggregation and platelet adherence to the subendothelium. Blood 1984; 63: 1408-1415
- 41 Thomas JE, Peake IR, Giddings JC, Welch AN, Bloom AL. The application of a monoclonal antibody to factor VIII related antigen (VIII: RAg) in immunoradiometric assays for factor VIII. Thromb Haemostas 1985; 53: 143-147