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Thromb Haemost 1977; 38(03): 0707-0716
DOI: 10.1055/s-0038-1651887
Original Article
Schattauer GmbH

Studies on the Neutralization of Rabbit Antibodies to Human Factor VIII

P. B. A Kernoff   *
1   Oxford Haemophilia Centre, Churchill Hospital, Oxford, OX3 7LJ, England
,
A. C Kaelin   **
1   Oxford Haemophilia Centre, Churchill Hospital, Oxford, OX3 7LJ, England
› Author Affiliations
Further Information

Publication History

Received 19 April 1977

Accepted 20 May 1977

Publication Date:
04 July 2018 (online)

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Summary

The capacity of normal and haemophilic cryoprecipitates to neutralize the anticoagulant effect of rabbit antibodies to human factor VIII (anti-VIII) was assessed using a quantitative estimation of antibody. About 4 times as much anti-VIII could be neutralized by normal factor VIII as was required to neutralize clotting activity. This suggests that there are probably several antigenic sites intimately associated with factor VIII clotting activity, quite apart from any antigenic sites which may be detected using antibodies directed against other components of the factor VIII complex. The neutralizing capacity of factor VIII was only slightly greater for the rabbit antibodies employed in this study than has been previously reported for antibodies of human origin, thus indicating only minor differences in specificities. Additional evidence in support of this concept was the finding that cryoprecipitates prepared from haemophilic plasmas previously recognized as either lacking or possessing the capacity to neutralize antibodies of human origin neutralized least or most quantities of rabbit antibodies, respectively.

* Present address: Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th St., New York, N. Y. 10032, U.S.A.


** Clinical Research Center, Watford Road, Harrow, Middlesex HAI 3UJ, England.


 

  • References

  • 1 Adelson E, Rheingold J. J, Parker O, Steiner M, Kirby J. C. 1963; The survival of factor VIII (anti-hemophilic globulin) and factor IX (plasma thromboplastin component) in normal humans. Journal of Clinical Investigation 42: 1040.
    CrossrefPubMedGoogle Scholar
  • 2 Bennett E, Huehns E. R. 1970; Immunological differentiation of three types of haemophilia and identification of some female carriers. Lancet II: 956.
    PubMedGoogle Scholar
  • 3 Berglund G. 1962; Studies of the inhibitory activity of specific antisera to some clotting factors in human plasma. British Journal of Haematology 8: 204.
    CrossrefPubMedGoogle Scholar
  • 4 Biggs R. 1974; The absorption of human factor VIII neutralizing antibody by factor VIII. British Journal of Haematology 26: 259.
    CrossrefPubMedGoogle Scholar
  • 5 Biggs R, Austen D. E. G, Denson K. W. E, Borrett R, Rizza C. R. 1972; The mode of action of antibodies which destroy factor VIII. II. Antibodies which give complex concentration graphs. British Journal of Haematology 23: 137.
    CrossrefPubMedGoogle Scholar
  • 6 Bouma B. N, van Mourik J. A, de Graaf S, Horduk-Hos J. M, Sixma J. J. 1976; Immunologic studies on human factor VIII (anti-hemophilic factor A, AHF) components produced by low-ionic-strength dialysis. Blood 47: 253.
    PubMedGoogle Scholar
  • 7 Denson K. W. E. 1976. a Appendix. In: Biggs R. (ed.) Human Blood Coagulation, Haemostasis and Thrombosis. 2nd edn.. Blackwell Scientific Publications; Oxford: 684.
    Google Scholar
  • 8 Denson K. W. E. 1976. b Abnormal clotting factors. In: Biggs R. (ed.) Human Blood Coagulation, Haemostasis and Thrombosis. 2nd edn.. Blackwell Scientific Publications; Oxford: 213.
    Google Scholar
  • 9 Denson K. W. E, Biggs R. 1976. Laboratory diagnosis, tests of clotting function and their standardization. In: Biggs R. (ed.) Human Blood Coagulation, Haemostasis and Thrombosis. 2nd edn.. Blackwell Scientific Publications; Oxford: 355.
    Google Scholar
  • 10 Denson K. W. E, Biggs R, Haddon M. E, Borrett R, Cobb K. 1969; Two types of haemophilia (A+ and A−): a study of 48 cases. British Journal of Haematology 17: 163.
    CrossrefPubMedGoogle Scholar
  • 11 Feinstein D, Chong M. N. Y, Kasper C. K, Rapaport S. I. 1969; Hemophilia A: polymorphism detectable by a factor VIII antibody. Science 163: 1071.
    CrossrefPubMedGoogle Scholar
  • 12 Gralnick H. R, Abrell E, Bagley J. 1971; Immunological studies of factor VIII (antihaemophiliac globulin) in haemophilia. A. Nature New Biology 230: 16.
    PubMedGoogle Scholar
  • 13 Gralnick H. R, Coller B. S, Marchesi S. L. 1973; Immunological studies of factor VIII in haemophilia and von Willebrand’s disease. Nature New Biology 244: 281.
    CrossrefPubMedGoogle Scholar
  • 14 Hoyer L. W. 1973; Immunologic properties of antihemophilic factor. Progressin Hematology 8: 191.
    PubMedGoogle Scholar
  • 15 Hoyer L. W, Breckenridge R. T. 1968; Immunologic studies of antihemophilic factor (AHF, factor VIII): Cross-reacting material in a genetic variant of hemophilia A. Blood 32: 962.
    PubMedGoogle Scholar
  • 16 Hoyer L. W, Breckenridge R. T. 1970; Immunologic studies of antihemophilic factor (AHF, factor VIII): II. Properties of cross-reacting material. Blood 35: 809.
    PubMedGoogle Scholar
  • 17 Kernoff P. B. A. 1974. The factor VUI-related antigen and antibodies to factor VIII. M.D. thesis University of London.;
    Google Scholar
  • 18 Kernoff P. B. A, Rizza C. R. 1973; The specificity of antibodies to factor VIII produced in the rabbit after immunization with human cryopredpitate. Thrombosis et Diathesis Haemorrhagica 29: 652.
    PubMedGoogle Scholar
  • 19 Lechner K. 1972; Inactive factor VIII in Hemophilia A and Willebrand’s disease. Acta Haematologica 48: 257.
    CrossrefPubMedGoogle Scholar
  • 20 McLester W. D, Wagner R. H. 1965; Antibody to antihemophilic factor and its lack of reaction with hemophilic plasma. American Journal of Physiology 208: 499.
    PubMedGoogle Scholar
  • 21 Meyer D, Dray L, Larrieu M. J. 1970; Hémophilie. Les variants des facteurs VIII et IX. Nouvelle revue Française d’hématologie 10: 619.
    PubMedGoogle Scholar
  • 22 Muntz R. H, Ekert H. 1973; Antibodies to factor VIII. (letter). Lancet II: 160.
    PubMedGoogle Scholar
  • 23 Newman J, Johnson A. J, Karpatkin M. H, Puszkin S. 1971; Methods for the production of clinically effective intermediate and high-purity factor-VIII concentrates. British Journal of Haematology 21: 1.
    CrossrefPubMedGoogle Scholar
  • 24 Piper W, Schreeer M. H. 1964; Über den immunologischen Nachweis von Faktor VIII-Protein im Bluterplasma und seine Bedeutung für das Verständnis der Hämophilie A. Thrombosis et Diathesis Haemorrhagica 11: 423.
    PubMedGoogle Scholar
  • 25 Pool J, Biggs R, Miller R. G. 1976; The estimation of the number of binding sites for antibody on antigen molecules with reference to factor VIII and its antibody. Thrombosis and Haemostasis 35: 274.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Rizza C. R, Biggs R. 1973; The treatment of patients who have factor VIII antibodies. British Journal of Haematology 24: 65.
    CrossrefPubMedGoogle Scholar
  • 27 Shanberge J. M, Gore I. 1957; Studies on the immunologic and physiologic activities of antihemophilic factor (AHF). Journal Laboratory and Clinical Medicine 50: 954.
    PubMedGoogle Scholar
  • 28 Sthes D. P, Hershgold E. J, Perlman J. D, Fudenberg H. H. 1971; Factor VIII detection by hemagglutination inhibition: hemophilia A and von Willebrand’s disease. Science 171: 196.
    CrossrefPubMedGoogle Scholar
  • 29 Thomopoulos D, Gardikas C. 1972; The two forms of haemophilia A in a population of Greek haemophiliacs. Journal of Clinical Pathology 25: 459.
    CrossrefPubMedGoogle Scholar
  • 30 Uszyński L. 1966; The immunological properties of factor VIII. I. Studies on the inhibitory activity of specific antisera to human antihemophilic globulin. Thrombosis et Diathesis Haemorrhagica 16: 559.
    PubMedGoogle Scholar
  • 31 Zimmerman T. S, Edgington T. S. 1974; Molecular immunology of factor VIII. Annual Review of Medicine 25: 303.
    CrossrefPubMedGoogle Scholar
  • 32 Zimmerman T. S, Ratnoff O. D, Powell A. E. 1971; Immunologic differentiation of classic hemophilia (Factor VIII deficiency) and von Willebrand’s disease. Journal of Clinical Investigation 50: 244.
    CrossrefPubMedGoogle Scholar