title: Using monoclonal antibodies as an international standard for the measurement of anti-adalimumab antibodies.
abstract: Comparing studies investigating anti-drug antibody (ADA) formation is hampered by the lack of comparability between study protocols, assay formats, and standardized reference materials. In this respect, the use of an international standard would mean a major step forward. Here we compared 11 fully human monoclonal antibodies against adalimumab in two assays commonly used for ADA measurement; the bridging ELISA and the antigen binding test (ABT). Our results show non-parallel titration of the monoclonal antibodies in both assays, which we also find for polyclonal ADA sources. Moreover, we observed that the output of the bridging ELISA depends to a large degree on the affinity of the monoclonal antibody. For the ABT, results reflect a combination of affinity and avidity. This suggests that rather than reporting ADA values in nanogram per milliliter, arbitrary units may be more appropriate. Together our data highlight the difficulty of ADA standardization by identifying several pitfalls that should be taken into account when selecting a standard for ADA testing.
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Pauline A
authors.initials: PA
authors.lastname: van Schouwenburg
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Kruithof
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands; Jan van Breemen Research Institute, Reade, Amsterdam, The Netherlands.
authors.forename: Gertjan
authors.initials: G
authors.lastname: Wolbink
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands. Electronic address: t.rispens@sanquin.nl.
authors.forename: Theo
authors.initials: T
authors.lastname: Rispens
mesh_terms: D000068879:Adalimumab / Q000097:blood*; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D011485:Protein Binding / Q000502:physiology; D012015:Reference Standards
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D000068879:Adalimumab
keywords: Adalimumab; Anti-drug antibodies; Anti-idiotype Antibodies; Human monoclonal antibodies; Immunogenicity