title: Lack of immune response to mouse IgG in hemophilia A patients treated chronically with Monoclate, a monoclonal antibody affinity purified factor VIII preparation.
abstract: Hemophilia A is caused by factor VIII deficiency that historically has been treated with either a cryoprecipitate fraction of serum or factor VIII concentrate. Recently, the availability of affinity isolated factor VIII (Monoclate) has allowed for a highly purified preparation for the chronic therapy of hemophilia A. This factor VIII preparation contains a trace quantity (less than 50 ng/100 I. U.) of mouse IgG. Immunoassays for the measurement of human IgG, IgM and IgE anti-mouse IgG antibody (HAMA) were developed and used to measure HAMA levels in hemophilia A patients undergoing chronic therapy with Monoclate in three different clinical studies. Natural antibodies to mouse IgG were observed in patient sera prior to Monoclate infusion. Data is presented demonstrating that induction of HAMA upon Monoclate treatment does not occur. The low level of mouse IgG contained in Monoclate appears to be below the threshold of immunogenicity. Most importantly, clinical symptoms related to hypersensitivity or anaphylaxis were never observed in any patient undergoing chronic therapy with Monoclate in these clinical studies.
authors.affiliation: Rorer Central Research, King of Prussia, PA 19406.
authors.forename: H M
authors.initials: HM
authors.lastname: Davis
authors.forename: S K
authors.initials: SK
authors.lastname: Brown
authors.forename: D W
authors.initials: DW
authors.lastname: Nash
authors.forename: A M
authors.initials: AM
authors.lastname: Pennetti
authors.forename: P M
authors.initials: PM
authors.lastname: Salzman
authors.forename: A B
authors.initials: AB
authors.lastname: Schreiber
authors.forename: J
authors.initials: J
authors.lastname: Haimovich
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D002675:Child, Preschool; D005169:Factor VIII / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006679:HIV Seropositivity / Q000453:epidemiology / Q000276:immunology; D006467:Hemophilia A / Q000188:drug therapy / Q000276:immunology*; D006526:Hepatitis C / Q000209:etiology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis; D015592:Immunoradiometric Assay; D007223:Infant; D008297:Male; D051379:Mice; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012217:Rheumatoid Factor / Q000032:analysis; D013997:Time Factors
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D005169:Factor VIII; D012217:Rheumatoid Factor