The Immunological Characterization of Human Antibodies to Factor VIII Isolated by Immuno-Affinity Chromatography

Summary

Nine human antibodies to factor VIII were isolated from haemophilic plasmas by affinity chromatography and gel filtration and six were subsequently subjected to immunological characterization. Three partially purified preparations were similarly characterized. Eight of the antibodies were characterized as being exclusively IgG and one preparation was found to contain IgM. Seven of the antibodies contained only a single light chain type, four being of type lambda and three of type kappa. Two antibody preparations contained both kappa and lambda light chains. In four of the preparations, only a single heavy chain sub-class could be demonstrated, three of IgG3 and one of IgG4. Of the remainder, three were a mixture of IgG3 and IgG4 sub-classes and one contained both IgG2 and IgG4. IgG sub-classification could not be achieved with the IgM-containing preparation. These results demonstrate a restricted heterogeneity of light and heavy chains in human antibodies to factor VIII.

Keywords

Factor VIII - Human antibodies to factor VIII - Antibody characterization

• References

• 1 Bidwell E, Denson KW E, Dike GW R, Augustin R, Lloyd GM. Antibody nature of the inhibitor to antihaemophilic globulin (factor VIII). Nature 1966; 210: 746-747
• 2 Shapiro S. The immunologic character of acquired inhibitors of antihemophilic globulin (factor VIII) and the kinetics of their interaction with factor VIII. J Clin Invest 1967; 46: 147-156
• 3 Feinstein D, Rapaport S, Chong M. Immunological characterization of 12 factor VIII inhibitors. Blood 1969; 34: 85-90
• 4 Robboy S, Lewis E, Schur P, Colman R. Circulating anticoagulants to factor VIII. Immunochemical studies and clinical response to factor VIII concentrates. Amer J Med 1970; 49: 740-752
• 5 Anderson B, Terry W. Gamma G4-globulin antibody causing inhibition of clotting factor VIII. Nature 1968; 217: 174-175
• 6 Shapiro S, Carrol KS. Acquired factor VIII antibodies: further immunologic and electrophoretic studies. Science 1968; 160: 786-787
• 7 Shulman NR, Hirshman RJ. Acquired hemophilia. Trans Assoc Am Physicians 1969; 82: 388-397
• 8 Poon M-C, Wine AC, Ratnoff OD, Bervier GM. Heterogeneity of human circulating anticoagulants against antihemophilic factor (factor VIII). Blood 1975; 46: 409-416
• 9 Lavergne JM, Meyer D, Reisner H. Characterization of human antifactor VIII antibodies purified by immune complex formation. Blood 1976; 48: 931-939
• 10 Rizza CR, Biggs R. The treatment of patients who have factor VIII antibodies. Brit J Haemat 1973; 24: 65-82
• 11 Zimmerman T, Ratnoff O, Powell A. Immunologic differentiation of classic hemophilia (factor VIII deficiency) and von Willebrand’s disease. J Clin Invest 1971; 50: 244-254
• 12 Fine JM, Steinbuch MA. A simple technique for the isolation of monoclonal IgG and IgA. Eur J Clin Biol Research 1970; 15: 1115-1121
• 13 March S, Parikh I, Cuatrecasas P. A simplified method for the CNBr activation of agarose for affinity chromatography. Anal Biochem 1974; 60: 149-152
• 14 Hardisty RH, MacPherson JF. A one-stage factor VIII (antihaemophilic globulin) assay and its use on venous and capillary plasma or blood. Thrombos Diath Haemorrh 1962; 07: 215-228
• 15 Lazarchick J, Hoyer LW. The properties of immune complexes formed by human antibodies to factor VIII. J Clin Invest 1977; 60: 1070-1079
• 16 Hong R. The Immunoglobulins. In: Clinical immunobiology. 1972. Vol 01. 29-46 Bach FH, Good RA. Eds Academic Press; London:
• 17 Graham JE, Yount WJ, Roberts HR. Immunochemical characterization of a human antibody to factor XIII. Blood 1973; 41: 661-669
• 18 Castaldi P, Penny R. A macroglobulin with inhibitory activity against coagulation factor VIII. Blood 1970; 35: 370-376
• 19 McKelvey E, Kwaan H. An IgM circulating anticoagulant with factor Vni inhibitory activity. Ann Intern Med 1972; 77: 571-575
• 20 Lusher JM, Shuster J, Evans RK, Poulik MD. Antibody nature of an AHG (factor VIII) inhibitor. J Pediat 1968; 72: 325-331