title: Commercial IgG immunoglobulin preparations exhibit IgG and IgA autoantibody reactivity at pharmacologic but not at physiologic concentrations.
abstract: IgG immunoglobulin preparations have been increasingly utilized to treat a variety of diseases. Since disease response to this form of therapy in patients with abnormal autoimmune function is often evaluated through the subsequent investigation of autoantibody levels, it is possible that autoantibody positivities reflect autoantibody reactivity of circulating immunoglobulin preparations and not of the patient's inherent B-cell activity. We therefore investigated three commercially available IgG immunoglobulin preparations separately for IgG, IgM and IgA autoantibody reactivity to six phospholipid antigens, total histone and four histone subfractions, and four polynucleotides. Universally, all three preparations demonstrated considerable IgG antiphospholipid and antihistone reactivity at dilutions of up to 1:10(3) but not antipolynucleotide reactivity. Although no IgM reactivity was detected in any of the preparations, in all three preparations surprising IgA reactivity, especially with antihistone specificity, was detected. No autoantibody reactivity was detected at dilutions compatible with physiologic conditions in vivo. Identical observations were made for lupus anticoagulant reactivity, which was evaluated by activated partial thromboplastin time (APTT) and tissue thromboplastin inhibition (TTI). Since autoantibody reactivities and prolonged APTT assays are observed only at pharmacologic dilution levels, it is unlikely that the administration of IgG immunoglobulin preparation will affect the evaluation of autoantibody levels in patients undergoing such treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Mount Sinai Hospital Medical Center, Chicago, IL 60608.
authors.forename: N
authors.initials: N
authors.lastname: Gleicher
authors.forename: L
authors.initials: L
authors.lastname: Harlow
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D001779:Blood Coagulation Factors / Q000276:immunology; D006657:Histones / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000276:immunology; D016756:Immunoglobulins, Intravenous; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D016682:Lupus Coagulation Inhibitor; D010743:Phospholipids / Q000276:immunology; D011119:Polynucleotides / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001779:Blood Coagulation Factors; D006657:Histones; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D016756:Immunoglobulins, Intravenous; D016682:Lupus Coagulation Inhibitor; D010743:Phospholipids; D011119:Polynucleotides