title: Antibodies to constant domains of therapeutic monoclonal antibodies: anti-hinge antibodies in immunogenicity testing.
abstract: Rheumatoid factors are antibodies directed against IgG that may confound immunogenicity testing for therapeutic monoclonal antibodies. We developed antigen-binding assays to monitor anti-drug-antibody (ADA) responses against infliximab and adalimumab using F(ab')2 fragments of the drug. This avoids possible detection of rheumatoid factor activity. During development of these assays, a number of sera from patients before treatment as well as several healthy control sera were tested positive. None of these sera contained antibodies specific for the therapeutic mAb. Instead, they were found to contain anti-hinge antibodies. We demonstrate that this aspecific antibody binding can be inhibited by adding F(ab')2 of intravenous immunoglobulin (IVIG), which consists of pooled polyclonal IgG derived from plasma. Using this protocol, anti-infliximab antibodies can be measured specifically without interference by anti-hinge antibodies.
authors: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands. t.rispens@sanquin.nl
authors: Theo
authors: T
authors: Rispens
authors: Henk
authors: H
authors: de Vrieze
authors: Els
authors: E
authors: de Groot
authors: Diana
authors: D
authors: Wouters
authors: Steven
authors: S
authors: Stapel
authors: Gerrit J
authors: GJ
authors: Wolbink
authors: Lucien A
authors: LA
authors: Aarden
mesh_terms: D000068879:Adalimumab; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000276:immunology; D007159:Immunologic Tests / Q000379:methods*; D000069285:Infliximab; D017434:Protein Structure, Tertiary; D012217:Rheumatoid Factor / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D012217:Rheumatoid Factor; D000069285:Infliximab; D000068879:Adalimumab