Characteristics, Mechanisms of Action, and Epitope Mapping of Anti-factor VIII Antibodies

Overview

Journal Clin Rev Allergy Immunol

Specialty Allergy & Immunology

Date 2009 Jan 28

PMID 19172415

Citations 8

Authors

Geraldine Lavigne-Lissalde

Chantal Rothschild

Claire Pouplard

Priscilla Lapalud

Yves Gruel

Jean-Francois Schved

Claude Granier

Affiliations

Soon will be listed here.

Abstract

The development of anti-factor VIII (FVIII) antibodies (Abs), also called inhibitors, is currently one of the most serious complications arising during the treatment of hemophilia A patients. Improved prevention and eradication of these Abs remain a challenge both for clinicians and scientists. Numerous studies in the literature have reported on their epitope specificity, on their mechanism of FVIII inactivation, as well as on the methods used for their detection. In this review, we summarize the current knowledge on the nature (isotypes, kinetic properties), epitope properties, and mechanisms of action of anti-FVIII Abs. Furthermore, we present methods for detection and epitope characterization of anti-FVIII Abs with emphasis on the Luminex technique susceptible to facilitate the monitoring of changes in the epitope specificity of these Abs.

Citing Articles

Predicting inhibitor development using a random peptide phage-display library approach in the SIPPET cohort.

Hassan S, Baselli G, Mollica L, Rossi R, Chand H, El-Beshlawy A Blood Adv. 2024; 8(11):2880-2889.

PMID: 38593222 PMC: 11176960. DOI: 10.1182/bloodadvances.2023011388.

Induction of long-term tolerance to a specific antigen using anti-CD3 lipid nanoparticles following gene therapy.

Chen C, Vander Kooi A, Cavedon A, Cai X, Hoggatt J, Martini P Mol Ther Nucleic Acids. 2023; 34:102043.

PMID: 37920545 PMC: 10618827. DOI: 10.1016/j.omtn.2023.102043.

Hemophilia a patients with inhibitors: Mechanistic insights and novel therapeutic implications.

Luo L, Zheng Q, Chen Z, Huang M, Fu L, Hu J Front Immunol. 2022; 13:1019275.

PMID: 36569839 PMC: 9774473. DOI: 10.3389/fimmu.2022.1019275.

Impact of different factor VIII inhibitor kinetic profiles on the inhibitor titer quantification using the modified Nijmegen-Bethesda assay.

Ketteler C, Hoffmann I, Davidson S, Chen D, Tiede A, Richter N Res Pract Thromb Haemost. 2022; 6(8):e12799.

PMID: 36518189 PMC: 9743337. DOI: 10.1002/rth2.12799.

Tolerating Factor VIII: Recent Progress.

Lacroix-Desmazes S, Voorberg J, Lillicrap D, Scott D, Pratt K Front Immunol. 2020; 10:2991.

PMID: 31998296 PMC: 6965068. DOI: 10.3389/fimmu.2019.02991.

References

Healey J, Barrow R, Tamim H, Lubin I, Shima M, Scandella D . Residues Glu2181-Val2243 contain a major determinant of the inhibitory epitope in the C2 domain of human factor VIII. Blood. 1998; 92(10):3701-9. View

Scandella D, Mattingly M, Prescott R . A recombinant factor VIII A2 domain polypeptide quantitatively neutralizes human inhibitor antibodies that bind to A2. Blood. 1993; 82(6):1767-75. View

Lavigne-Lissalde G, Tarrade C, Lapalud P, Chtourou S, Schved J, Granier C . Simultaneous detection and epitope mapping of anti-factor VIII antibodies. Thromb Haemost. 2008; 99(6):1090-6. DOI: 10.1160/TH07-08-0497. View

Kessler C . Acquired factor VIII autoantibody inhibitors: current concepts and potential therapeutic strategies for the future. Haematologica. 2001; 85(10 Suppl):57-61; discussion 61-3. View

Shetty S, Ghosh K, Mohanty D . An ELISA assay for the detection of factor VIII antibodies - comparison with the conventional Bethesda assay in a large cohort of haemophilia samples. Acta Haematol. 2002; 109(1):18-22. DOI: 10.1159/000067272. View

Goudemand J, Laurian Y, Calvez T . Risk of inhibitors in haemophilia and the type of factor replacement. Curr Opin Hematol. 2006; 13(5):316-22. DOI: 10.1097/01.moh.0000239702.40297.ec. View

Spiegel Jr P, Jacquemin M, Saint-Remy J, Stoddard B, Pratt K . Structure of a factor VIII C2 domain-immunoglobulin G4kappa Fab complex: identification of an inhibitory antibody epitope on the surface of factor VIII. Blood. 2001; 98(1):13-9. DOI: 10.1182/blood.v98.1.13. View

Hsu T, Pratt K, Thompson A . The factor VIII C1 domain contributes to platelet binding. Blood. 2007; 111(1):200-8. PMC: 2200805. DOI: 10.1182/blood-2007-01-068957. View

Hay C, Ludlam C, Colvin B, Hill F, Preston F, Wasseem N . Factor VIII inhibitors in mild and moderate-severity haemophilia A. UK Haemophilia Centre Directors Organisation. Thromb Haemost. 1998; 79(4):762-6. View

10.

Saenko E, Shima M, Rajalakshmi K, Scandella D . A role for the C2 domain of factor VIII in binding to von Willebrand factor. J Biol Chem. 1994; 269(15):11601-5. View

11.

Eaton D, Rodriguez H, Vehar G . Proteolytic processing of human factor VIII. Correlation of specific cleavages by thrombin, factor Xa, and activated protein C with activation and inactivation of factor VIII coagulant activity. Biochemistry. 1986; 25(2):505-12. DOI: 10.1021/bi00350a035. View

12.

Zhong D, Saenko E, Shima M, Felch M, Scandella D . Some human inhibitor antibodies interfere with factor VIII binding to factor IX. Blood. 1998; 92(1):136-42. View

13.

Scandella D, DeGraaf Mahoney S, Mattingly M, ROEDER D, Timmons L, Fulcher C . Epitope mapping of human factor VIII inhibitor antibodies by deletion analysis of factor VIII fragments expressed in Escherichia coli. Proc Natl Acad Sci U S A. 1988; 85(16):6152-6. PMC: 281923. DOI: 10.1073/pnas.85.16.6152. View

14.

Goudemand J, Rothschild C, Demiguel V, Vinciguerrat C, Lambert T, Chambost H . Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A. Blood. 2005; 107(1):46-51. DOI: 10.1182/blood-2005-04-1371. View

15.

Lacroix-Desmazes S, Wootla B, Dasgupta S, Delignat S, Bayry J, Reinbolt J . Catalytic IgG from patients with hemophilia A inactivate therapeutic factor VIII. J Immunol. 2006; 177(2):1355-63. DOI: 10.4049/jimmunol.177.2.1355. View

16.

Mondorf W, Klinge J, Luban N, Bray G, Saenko E, Scandella D . Low factor VIII recovery in haemophilia A patients without inhibitor titre is not due to the presence of anti-factor VIII antibodies undetectable by the Bethesda assay. Haemophilia. 2001; 7(1):13-9. DOI: 10.1046/j.1365-2516.2001.00463.x. View

17.

Scandella D, Gilbert G, Shima M, Nakai H, Eagleson C, Felch M . Some factor VIII inhibitor antibodies recognize a common epitope corresponding to C2 domain amino acids 2248 through 2312, which overlap a phospholipid-binding site. Blood. 1995; 86(5):1811-9. View

18.

DiMichele D, Kroner B . Analysis of the North American Immune Tolerance Registry (NAITR) 1993-1997: current practice implications. ISTH Factor VIII/IX Subcommittee Members. Vox Sang. 1999; 77 Suppl 1:31-2. DOI: 10.1159/000056712. View

19.

Martin P, Sukhu K, Chambers E, Giangrande P . Evaluation of a novel ELISA screening test for detection of factor VIII inhibitory antibodies in haemophiliacs. Clin Lab Haematol. 1999; 21(2):125-8. DOI: 10.1046/j.1365-2257.1999.00194.x. View

20.

Albert T, Lange S, Oldenburg J, Graw J, Schramm W, Hanfland P . [Characterization of factor VIII antibody epitopes from haemophilia A patients using cellulose bound FVIII peptide libraries]. Hamostaseologie. 2003; 23(1):13-7. View