Inhibitor Binding Affnity (IBA)
The IBA study is carried out in the laboratory of Dr. C. Kannicht and Dr. G. Kohla in Berlin, Germany.
The aims of this study are to evaluate:
- a possible correlation of anti-FVIII antibody affnities and success of ITI-treatment;
- and to generate complementary data to antibody epitope mapping and inhibitory activity determination;
- a possible correlation of antibody binding epitope, binding affnity and inhibitory activity;
- a possible correlation of antibody affnity, FVIII recovery and success of ITI-treatment;
In a frst step, plasma sample IgG will be purifed using the Melon Gel IgG Purifcation System. The amount of FVIII-binding IgG will be determined by CFCA or ELISA. Finally, affnity measurements will be done by surface plasmon resonance (SPR). Affnities will be calculated using the BiaEval-Software.
Literature overview:
- Butenas S et al. Product-dependent anti-factor VIII antibodies, Haemophilia 2013; 19:619-625.
- Egler C et al. Kinetic parameters of monoclonal antibodies ESH2, ESH4, ESH5, and ESH8 on coagulation factor VIII and their influence on factor VIII activity. J Mol Recognit 2009; 22:301-306.
- Hofbauer CJ et al. Affnity of FVIII-specifc antibodies reveals major differences between neutralizing and non-neutralizing antibodies. Blood 2015; 125 (7): 1180-8
- Karlsson R et al. Analyzing a kinetic titration series using affnity biosensors. Anal Biochem 2006; 349: 136-147
- Whelan SF et al. Distinct characteristics of antibody responses against factor VIII in healthy individuals and in different cohorts of hemophilia A patients. Blood 2013; 121: 1039-48