Thursday, October 24, 2013
This week in techniques
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Algorithm to predict risk
of developing neutralizing antibodies to factor
A computational algorithm
to predict the risk of developing factor VIII-neutralizing inhibitory
antibodies could help guide the treatment of patients with hemophilia A.
Sequencing and gene expression analysis of samples from patients who have
hemophilia A caused by intron 22 inverted (I22I) factor VIII found
that the entire factor VIII protein was expressed as two polypeptides, which
explains why patients carrying this inversion have decreased risk of
developing inhibitory antibodies against factor VIII replacement therapy
compared with patients who have factor VIII deletions. A computational
algorithm that analyzes the affinity of major
histocompatibility complex class II (MHCII)
for foreign peptides was developed. The algorithm was used to predict whether
differences between recombinant factor VIII products and patient-encoded I22I
factor VIII would lead to inhibitor development. Next steps include applying
this algorithm to analyze the immune response to other foreign peptides.
Published online Oct. 24, 2013
Patent applications filed
covering the development of personalized factor VIII replacement therapies;
licensed to Haplomics
Pandey, G.S. et al. Nat.
Med.; published online Sept. 15, 2013;
Contact: Zuben E. Sauna, Food and Drug Administration,
Contact: Tom E. Howard, VA Greater Los Angeles Healthcare
System, Los Angeles, Calif.
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