Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Anders Larsson, Uppsala University, Sweden
- Second opponent: Chief Physician Christian Löwbeer, SYNLAB Medilab, Sweden
- Third member and chair of the evaluation committee: Professor Heidi Kiil Blomhoff, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor Øyvind Bruland, Faculty of Medicine, University of Oslo
Principal Supervisor
Professor Trine Bjøro, Faculty of Medicine, University of Oslo
Summary
Monoclonal and polyclonal antibodies from animals are used in immunological assays to measure concentrations of many clinically relevant proteins, peptides and drugs in blood samples. Heterophilic antibodies are immunoglobulins (present in some blood samples) that bind to the animal antibodies used in immunoassays. This type of assay interference is usually called heterophilic antibody interference. In some cases, false results caused by such interference may go undetected and lead to unnecessary diagnostic and potentially harmful therapeutic interventions, and immunoassay companies invest substantial resources to make their assays resilient to antibody interference. Heterophilic antibodies are found in the blood of both patients and healthy individuals, and are only rarely associated with prior exposure to animal antibodies. While some patient groups have an increased risk of antibody-mediated interference, particularly patients with seropositive rheumatoid arthritis, it is difficult to suspect assay interference before it appears.
Bolstad and colleagues tested how resistant 170 commercially available immunoassay kits were to heterophilic antibody interference, and found that 21 assays lacked adequate protection against Fc-reactive heterophilic antibodies, which is the most common reactivity associated with heterophilic antibodies. Since the results were published, several of these vulnerable assays have been relaunched with improved protection against heterophilic antibody interference. Continued focus was put on improving execution and interpretation of tests to detect interference, but also to develop strategies to limit the damage from heterophilic antibodies relevant to both clinical laboratories and immunoassay developers. Finally, the prevalence of heterophilic antibodies in patient samples was examined by screening more than 5000 blood samples in an in house assay designed to detect reactivities to eight different animal antibodies used in immunoassays. Candidate samples identified in the screening assay were subsequently tested in a range of individual assays to identify the individual reactivities in each sample. Heterophilic antibodies with reactivity to rabbit IgG (5.5 %) and murine IgG1 (4.8 %) were the most common, while reactivity to murine IgG2a (0.1 %), murine IgG2b (0.6 %), goat and sheep IgG (both 0.2 %) was rare. When specific blocking of the commonly occurring anti-bovine antibodies was lifted, vast cross-reactivity to sheep and goat IgG was evident. These findings should enable immunoassay developers to further improve protection against heterophilic antibodies in immunoassays, thereby reducing the risk of unnecessary harm to patients.
Additional information
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