FVIII inhibitor epitope mapping

Do FVIII inhibitor epitopes impact response to ITI?

FVIII inhibitors bind to different regions, or epitopes, of the FVIII protein.

Examples of FVIII epitopes recognised by neutralising antibodies

Screenshot 259

There is some evidence that the specificity of inhibitors to certain domains on the FVIII protein could be related to ITI outcome. For example, higher levels of antibodies to the A1 and A2 domains prior to ITI start have been suggested to be predictive of ITI failure2.

In addition to this domain level mapping, specific epitopes within the A2, C1 and C2 domains may affect response to treatment with factor VIII3-6.

The distribution of immunoglobulin (Ig) subclasses of the antibodies during ITI may also be associated with ITI outcome. IgG4 antibodies have been shown to be more prominent in patients with high-titre inhibitors who needed longer ITI treatment or who failed ITI7.

MOTIVATE will investigate whether FVIII inhibitor epitope mapping can help to predict treatment outcome. For patients who have detectable antibodies to the A2, C1 or C2 domain, MOTIVATE will map their antibodies to epitopes within those domains.

FVIII inhibitor epitope mapping sub-study

Sub-study lead investigators

whoweare JO profile v2

Johannes Oldenburg

Director, Institute for Experimental Haematology and Transfusion Medicine (IHT),
Bonn, Germany

whoweare BP profile v2

Behnaz Pezeshkpoor

Institute for Experimental Haematology and Transfusion Medicine (IHT),
Bonn, Germany

whoweare SM profile v3

Shannon Meeks

Associate Professor, Department of Pediatrics, Emory University School of Medicine,
Atlanta, GA, US

MOTIVATE will map the FVIII epitope spectrum of patients over time and assess the predictive capacity of epitope mapping for clinical outcomes.

substudy needs icon small

What is needed for this analysis?

A blood sample of 1 mL collected at baseline, 1 month after treatment start and every 4 months

    References:

  1. Pratt KP. <i>Cell Immunol</i> 2016; 301:12-7
  2. Lapalud P et al. <i>J Thromb Haemost</i> 2015; 13:540-7
  3. Eubanks J et al. <i>Blood</i> 2016; 127:2028-34
  4. Batsuli G et al. <i>Blood</i> 2016; 128:2055-67
  5. Meeks SL et al. <i>Blood</i> 2008; 112:1151-3
  6. Markovitz RC et al. <i>Blood</i> 2013; 121:2785-95
  7. van Helden PM et al. <i>Br J Haematol</i> 2008; 142:644-52

Contact