Abstract
The Factor VIII antigen molecules in the plasma of patients with classical type 1 and variant type 2A von Willebrand disease were compared to the Factor VIII antigen molecules in normal plasma. Factor VIII antigen was isolated from plasma by solid-phase immunoprecipitation and analyzed by NaDodSO4/polyacrylamide gel electrophoresis; the stained Factor VIII antigen bands were removed, radioiodinated, and subjected to tryptic digestion. Computerized analysis of autoradiographs revealed that the two-dimensional peptide maps of the different Factor VIII antigens were remarkably similar. The results suggest that the Factor VIII antigen molecules in these two forms of von Willebrand disease are probably identical to the Factor VIII antigen molecules present in normal plasma. It is thus likely that the differences observed in plasma Factor VIII antigen in classical and variant von Willebrand disease are not due to qualitatively abnormal molecules but rather represent quantitative shifts in the metabolism of normal Factor VIII antigen molecules.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allain J. P., Cooper H. A., Wagner R. H., Brinkhous K. M. Platelets fixed with paraformaldehyde: a new reagent for assay of von Willebrand factor and platelet aggregating factor. J Lab Clin Med. 1975 Feb;85(2):318–328. [PubMed] [Google Scholar]
- Anderson J. M. Structural studies on human spectrin. Comparison of subunits and fragmentation of native spectrin. J Biol Chem. 1979 Feb 10;254(3):939–944. [PubMed] [Google Scholar]
- Converse C. A., Papermaster D. S. Membrane protein analysis by two-dimensional immunoelectrophoresis. Science. 1975 Aug 8;189(4201):469–472. doi: 10.1126/science.1154021. [DOI] [PubMed] [Google Scholar]
- Ekert H., Chavin S. I. Changes in electrophoretic mobility of human factor VIII-related antigen: evidence for subunit structure. Br J Haematol. 1977 Jun;36(2):271–279. doi: 10.1111/j.1365-2141.1977.tb00648.x. [DOI] [PubMed] [Google Scholar]
- Elder J. H., Pickett R. A., 2nd, Hampton J., Lerner R. A. Radioiodination of proteins in single polyacrylamide gel slices. Tryptic peptide analysis of all the major members of complex multicomponent systems using microgram quantities of total protein. J Biol Chem. 1977 Sep 25;252(18):6510–6515. [PubMed] [Google Scholar]
- Gralnick H. R., Sultan Y., Coller B. S. Von Willebrand's disease: combined qualitative and quantitative abnormalities. N Engl J Med. 1977 May 5;296(18):1024–1030. doi: 10.1056/NEJM197705052961802. [DOI] [PubMed] [Google Scholar]
- Jaffe E. A., Nachman R. L. Subunit structure of factor VIII antigen synthesized by cultured human endothelial cells. J Clin Invest. 1975 Sep;56(3):698–702. doi: 10.1172/JCI108140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kernoff P. B., Gruson R., Rizza C. R. A variant of factor 8 related antigen. Br J Haematol. 1974 Mar;26(3):435–440. doi: 10.1111/j.1365-2141.1974.tb00484.x. [DOI] [PubMed] [Google Scholar]
- Kessler S. W. Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol. 1975 Dec;115(6):1617–1624. [PubMed] [Google Scholar]
- LAURELL C. B. ANTIGEN-ANTIBODY CROSSED ELECTROPHORESIS. Anal Biochem. 1965 Feb;10:358–361. doi: 10.1016/0003-2697(65)90278-2. [DOI] [PubMed] [Google Scholar]
- Meyer D., Obert B., Pietu G., Lavergne J. M., Zimmerman T. S. Multimeric structure of factor VIII/von Willebrand factor in von Willebrand's disease. J Lab Clin Med. 1980 Apr;95(4):590–602. [PubMed] [Google Scholar]
- Nachman R. L., Jaffe E. A., Ferris B. Peptide map analysis of normal plasma and platelet factor VIII antigen. Biochem Biophys Res Commun. 1980 Feb 27;92(4):1208–1214. doi: 10.1016/0006-291x(80)90415-5. [DOI] [PubMed] [Google Scholar]
- Over J., Bouma B. N., Sixma J. J., Bolhuis P. A., Vlooswijk R. A. Heterogeneity of human factor VIII. III. Transitions between forms of factor VIII present in cryoprecipitate and in cryosupernatant plasma. J Lab Clin Med. 1980 Mar;95(3):323–334. [PubMed] [Google Scholar]
- Over J., Sixma J. J., Bruïne M. H., Trieschnigg M. C., Vlooswijk R. A., Beeser-Visser N. H., Bouma B. N. Survival of 125iodine-labeled Factor VIII in normals and patients with classic hemophilia. Observations on the heterogeneity of human Factor VIII. J Clin Invest. 1978 Aug;62(2):223–234. doi: 10.1172/JCI109120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peake I. R., Bloom A. L., Giddings J. C. Inherited variants of factor-VIII-related protein in von Willebrand's disease. N Engl J Med. 1974 Jul 18;291(3):113–117. doi: 10.1056/NEJM197407182910301. [DOI] [PubMed] [Google Scholar]
- Ruggeri Z. M., Pareti F. I., Mannucci P. M., Ciavarella N., Zimmerman T. S. Heightened interaction between platelets and factor VIII/von Willebrand factor in a new subtype of von Willebrand's disease. N Engl J Med. 1980 May 8;302(19):1047–1051. doi: 10.1056/NEJM198005083021902. [DOI] [PubMed] [Google Scholar]
- Ruggeri Z. M., Zimmerman T. S. Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets. J Clin Invest. 1980 Jun;65(6):1318–1325. doi: 10.1172/JCI109795. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shoa'i I., Lavergne J. M., Ardaillou N., Obert B., Ala F., Meyer D. Heterogeneity of von Willebrand's disease: study of 40 Iranian cases. Br J Haematol. 1977 Sep;37(1):67–83. [PubMed] [Google Scholar]
- Sultan Y., Simeon J., Caen J. P. Electrophoretic heterogeneity of normal factor VIII/Von Willebrand protein, and abnormal electrophoretic mobility in patients with Von Willebrand's disease. J Lab Clin Med. 1976 Feb;87(2):185–194. [PubMed] [Google Scholar]
- Weinstein M. J., Deykin D., Davie E. W. Quantitative determination of factor-VIII protein by two-stage gel electrophoresis. Br J Haematol. 1976 Jul;33(3):343–355. doi: 10.1111/j.1365-2141.1976.tb03550.x. [DOI] [PubMed] [Google Scholar]
- Weiss H. J., Hoyer L. W., Rickles F. R., Varma A., Rogers J. Quantitative assay of a plasma factor deficient in von Willebrand's disease that is necessary for platelet aggregation. Relationship to factor VIII procoagulant activity and antigen content. J Clin Invest. 1973 Nov;52(11):2708–2716. doi: 10.1172/JCI107465. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zimmerman T. S., Abildgaard C. F., Meyer D. The factor VIII abnormality in severe von Willebrand's disease. N Engl J Med. 1979 Dec 13;301(24):1307–1310. doi: 10.1056/NEJM197912133012402. [DOI] [PubMed] [Google Scholar]
- Zimmerman T. S., Hoyer L. W., Dickson L., Edgington T. S. Determination of the von Willebrand's disease antigen (factor VIII-related antigen) in plasma by quantitative immunoelectrophoresis. J Lab Clin Med. 1975 Jul;86(1):152–159. [PubMed] [Google Scholar]
- Zimmerman T. S., Roberts J., Edgington T. S. Factor-VIII-related antigen: multiple molecular forms in human plasma. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5121–5125. doi: 10.1073/pnas.72.12.5121. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Mourik J. A., Bolhuis P. A. Dispersity of human factor VIII--Von Willebrand factor. Thromb Res. 1978 Jul;13(1):15–24. doi: 10.1016/0049-3848(78)90105-6. [DOI] [PubMed] [Google Scholar]
- van Mourik J. A., Bouma B. N., LaBruyère W. T., de Graaf S., Mochtar I. A. Factor VIII, a series of homologous oligomers and a complex of two proteins. Thromb Res. 1974 Jan;4(1):155–164. doi: 10.1016/0049-3848(74)90211-4. [DOI] [PubMed] [Google Scholar]