The development and characterisation of antibodies to human factor VIII in haemophilic dogs.
Four haemophilic dogs received infusions of human factor VIII concentrates, and developed inhibitors to human F VIII. These inhibitors cross-reacted with canine F VIII with parallel increases and decreases in titre. Cross-reaction was also found to porcine F VIII but changes in titre did not correlate with anti-human and anti-canine titres. These inhibitors were found to be immunoglobulins, and antibodies were detected against other proteins found in concentrates. Kinetic studies showed that in all four dogs the F VIII inhibitors were Type II antibodies. One of the dogs behaved as a "high-responder", whilst another was more analogous to a "low-responder" patient. Phospholipid protection experiments in vitro demonstrated that some antibodies could be prevented from inhibiting F VIII, and porcine F VIII was particularly well protected against inhibition.
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000302:isolation & purification*; D004285:Dogs / Q000276:immunology*; D005169:Factor VIII / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D007262:Infusions, Intravenous; D007700:Kinetics; D008297:Male; D010743:Phospholipids / Q000494:pharmacology / Q000627:therapeutic use; D013552:Swine
D000906:Antibodies; D010743:Phospholipids; D005169:Factor VIII