Antibodies to heterologous proteins in hemophilia A patients receiving recombinant factor VIII (Recombinate).
As a consequence of the manufacturing process, trace quantities of Chinese hamster ovary cell protein, bovine serum albumin and murine immunoglobulin G are present in Recombinate recombinant human factor VIII (rhFVIII). The development of antibodies (Abs) to these heterologous proteins was evaluated during long-term rhFVIII therapy of hemophilia A in 68 previously treated and 73 previously untreated patients. Ab prevalence was also assessed in 157 non-hemophilic subjects. Abs against heterologous proteins could be detected in varying percentages of patients and non-hemophilic subjects. Abs arose in patients sporadically, and levels were typically low. There were no adverse events associated with development or presence of anti-heterologous protein Abs. These data indicate that sustained immune responses to trace levels of heterologous proteins are very infrequent during long-term rhFVIII therapy.
Ingerslev
Jørgen
J
Center for Hemophilia and Thrombosis, Department of Clinical Immunology, University Hospital Skejby, Aarhus, Denmark.
Christiansen
Kirsten
K
Ravn
Hanne B
HB
Bray
Gordon L
GL
Gomperts
Edward D
ED
D000328:Adult; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000276:immunology; D000910:Antibodies, Heterophile / Q000096:biosynthesis / Q000276:immunology*; D000918:Antibody Specificity; D016466:CHO Cells / Q000276:immunology; D002417:Cattle / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D006224:Cricetinae; D003412:Cricetulus / Q000276:immunology*; D003470:Culture Media; D004340:Drug Contamination; D005169:Factor VIII / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D006467:Hemophilia A / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice / Q000276:immunology*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D012710:Serum Albumin, Bovine / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000910:Antibodies, Heterophile; D003470:Culture Media; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D012710:Serum Albumin, Bovine; C078147:F8 protein, human; D005169:Factor VIII