title: Immunological safety assessments of anti-IgE antibody which is detached from therapeutic immunoadsorbents for removing IgE.
abstract: Assessments were made of the safety of antibodies which might be detached from a therapeutic immunoadsorbent (IA) during extracorporeal circulation, with respect to possible immunological responses to such antibodies. The IA used was antihuman IgE antibody (a-IgE Ab) immobilized on a carrier, for removal of IgE from patients' plasma. The antibody was raised in goats and isolated to give an IgG fraction. This fraction was either used without further purification or was subjected to immunoaffinity purification. The active anaphylaxis test in guinea pigs indicated that positive responses were not observed at doses of less than 0.1 micrograms of goat IgG per animal. Rabbits given goat IgG intravenously 3 times a week for 8 weeks did not produce the specific antibody against goat IgG at doses of less than 0.05 micrograms/kg, which corresponds to less than 3 micrograms for an adult with a body weight of 60 kg. However, none of the rabbits given goat IgG at 2.5 mg/kg showed any toxic reactions and different patterns of the body weight growth from these in the control group. In addition, we tested whether immunoaffinity purified a-IgE Ab could trigger Type I hypersensitivity in a monkey model. Anaphylactic reactions were not observed after a single intravenous injection of a-IgE Ab at less than 10 micrograms/kg. These in vivo results are useful to judge whether the amount of antibody that leaks from a therapeutic IA is acceptable or not in a clinical situation.
authors.affiliation: Medical Supply and Equipment Department, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Kidaka
mesh_terms: D000707:Anaphylaxis / Q000209:etiology / Q000276:immunology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005990:Glycerol / Q000097:blood; D006041:Goats; D006168:Guinea Pigs; D006632:Histamine / Q000097:blood; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007164:Immunosorbents / Q000276:immunology* / Q000494:pharmacology; D008252:Macaca fascicularis; D011817:Rabbits; D012449:Safety
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D007164:Immunosorbents; D007073:Immunoglobulin E; D006632:Histamine; D005990:Glycerol