A microarray that can determine anti-fVIII Ab epitopes for hemophilia A patient personalized therapy planning.
- Has the potential to predict responses of patients with hemophilia A and inhibitors to fVIII infusions or combinations of fVIII and bypassing agents better than Ab titers alone.
- Has the potential to predict if patients will respond to ITI.
- The microarray uses minimal volume of patient plasma.
Patients with high inhibiter titers are felt to be unlikely to respond to fVIII infusions and some patients treated with bypassing agents do not respond well to the bypass therapy. The clinical method to eliminate fVIII Abs in these patients is immune tolerance induction (ITI), requiring intensive fVIII treatment until Abs titers drop. The treatment is costly and not every patient responds. Researchers at Emory University have developed a microarray that detects the presence and epitope coverage of anti-fVIII Abs in patient blood using minimal volumes of patient plasm. Sixteen anti-human fVIII murine monoclonal Abs with minimal overlapping epitopes are printed in triplicate on 8-pad nitrocellulose film slides. Patient plasma is mixed with biotin-conjugated fVIII and later loaded onto the slides. After washing and incubation with fluorescence-labeled streptavidin, the slides will be read by a fluoresence detector. Loss of signals at certain spots indicates loss of binding of fVIII to the printed Abs with certain epitopes, which reveals the presence of patient Abs with the same epitopes. This microarray uses minimal volume of patient plasma, which is important for routine clinical care in young children. This microarray can be used to determine if patients with certain Abs against specific epitopes will respond better to ITI than other patients.
Publication: Meeks et al., (2007). Blood 110:4234-4242