|
|
 Previous Article | Table of Contents | Next Article 
Immunoblot analysis shows changes in factor VIII inhibitor chain
specificity in factor VIII inhibitor patients over time
CA Fulcher, K Lechner and S de Graaf Mahoney
Department of Basic and Clinical Research, Scripps Clinic, La Jolla, CA
92037.
We have used immunoblotting of purified factor VIII (FVIII) to determine
whether or not changes in FVIII chain specificity occur during the course
of an inhibitor. Serial plasma samples from 15 inhibitor patients (13
hemophilic and two spontaneous) were analyzed. Nine of the 15 antibodies,
all with epitopes on the 44-kilodalton (Kd) thrombin fragment of the 92-Kd
FVIII heavy chain and/or the 72-Kd thrombin fragment of the 80-Kd FVIII
light chain, showed no change in FVIII chain specificity. However, six of
the inhibitors analyzed showed changes in FVIII fragment specificity. Four
inhibitors (three hemophilic and one spontaneous) reactive with 72-Kd
thrombin fragment also became reactive with the 44-Kd thrombin fragment
after an anamnestic response to FVIII infusion. Another inhibitor with
epitopes on both the 54-Kd and 44-Kd thrombin fragments lost most of its
reactivity with the 44-Kd fragment but retained its reactivity with the
54-Kd fragment following a FVIII infusion. The inhibitor later regained its
44-Kd-fragment reactivity but lost its 54-Kd-fragment reactivity following
treatment with FEIBA, FVIII inhibitor bypassing activity. The last
inhibitor studied had an antibody to either the 44-Kd fragment or to both
the 44-Kd and 72-Kd fragments during anamnestic responses to FVIII. These
data indicate that a FVIII inhibitor patient can potentially produce
antibody to multiple areas on the FVIII molecule and that this must be
taken into account in the design of specific therapeutic products.
Volume 72,
Issue 4,
pp. 1348-1356,
10/01/1988
Copyright © 1988 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Wootla, S. Dasgupta, J. D. Dimitrov, J. Bayry, H. Levesque, J.-Y. Borg, A. Borel-Derlon, D. N. Rao, A. Friboulet, S. V. Kaveri, et al.
Factor VIII Hydrolysis Mediated by Anti-Factor VIII Autoantibodies in Acquired Hemophilia
J. Immunol.,
June 1, 2008;
180(11):
7714 - 7720.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. D. Christophe, P. J. Lenting, G. Cherel, M. Boon-Spijker, J.-M. Lavergne, R. Boertjes, M.-E. Briquel, A. de Goede-Bolder, J. Goudemand, S. Gaillard, et al.
Functional mapping of anti-factor IX inhibitors developed in patients with severe hemophilia B
Blood,
September 1, 2001;
98(5):
1416 - 1423.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. F. Healey, R. T. Barrow, H. M. Tamim, I. M. Lubin, M. Shima, D. Scandella, and P. Lollar
Residues Glu2181-Val2243 Contain a Major Determinant of the Inhibitory Epitope in the C2 Domain of Human Factor VIII
Blood,
November 15, 1998;
92(10):
3701 - 3709.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Fijnvandraat, E. A.M. Turenhout, E. N. van den Brink, J. W. ten Cate, J. A. van Mourik, M. Peters, and J. Voorberg
The Missense Mutation Arg593 right-arrow Cys Is Related to Antibody Formation in a Patient With Mild Hemophilia A
Blood,
June 15, 1997;
89(12):
4371 - 4377.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Prescott, H. Nakai, E. L. Saenko, I. Scharrer, I. M. Nilsson, J. E. Humphries, D. Hurst, G. Bray, D. Scandella, and the Recombinate and Kogenate Study Groups
The Inhibitor Antibody Response Is More Complex in Hemophilia A Patients Than in Most Nonhemophiliacs With Factor VIII Autoantibodies
Blood,
May 15, 1997;
89(10):
3663 - 3671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
