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Doctoral thesis, 2020

Canine heterophilic antibodies

Bergman, Daniel


Anamnesis, physical examination and laboratory testing are the pillars of the clinical diagnostic procedure. Alas, laboratory tests are not perfect and analytical errors happen, which can lead to misdiagnosis and detrimental consequences for patient care. Immunoassays are commonly used to measure various hormones and disease markers in patient samples. Despite decades of methodological development and technological advances, immunoassays used for clinical diagnosis are still associated with limitations and even some flaws.

This thesis focuses on a long-lived immunoassay flaw that has been poorly researched in veterinary medicine. Humans and animals both carry heterophilic antibodies, also called anti-animal antibodies, in their circulation. These antibodies can interfere with immunoassays and cause erroneous results. The mechanism of action is the same for animals as it is for humans; the heterophilic antibodies bind to animal antibodies employed by the immunoassay, usually leading to a falsely increased measurement. Due to the extensive use of mouse IgG for analyte detection in immunoassays, anti-mouse antibodies are of particular concern.

Herein, the prevalence of heterophilic antibodies against mouse IgG in a cohort of dog patients is estimated. It is demonstrated that the antibodies can have tangible consequences for patient care as they can interfere with commercial immunoassays used in veterinary laboratories. Falsely increased anti-Müllerian hormone (AMH) measurements were found, which could lead to needless surgery in dog patients. The molecular characteristics of canine heterophilic antibodies were shown to be heterogeneous. They may react with the Fc region or the Fab region of the murine IgG molecule. There is cross-reactivity with IgG from several species, and heterophilic antibodies in dogs are made up of the IgA, IgG and IgM isotypes. The prevalence of the antibodies varies between dog breeds, and the Bernese mountain dog is tentatively predisposed to heterophilic antibodies. The origin of these antibodies remains mostly unclear, but there is occasional cross-reactivity between antibodies to mouse IgG and canine autoantibodies to IgG. Canine heterophilic antibodies can persist for at least two years in serum and represent a risk factor for repeated analytical errors and misdiagnosis in patients with these antibodies.


antibodies; anti-mouse antibodies; autoantibodies; autoimmunity; canine; ELISA; immunoassay; immunotherapy; interference; rheumatoid factors

Published in

Acta Universitatis Agriculturae Sueciae
2020, number: 2020:22
ISBN: 978-91-7760-562-1, eISBN: 978-91-7760-563-8
Publisher: Department of Clinical Sciences, Swedish University of Agricultural Sciences

Authors' information

Bergman, Daniel
Swedish University of Agricultural Sciences, Department of Clinical Sciences

UKÄ Subject classification

Clinical Science
Immunology in the medical area
Clinical Laboratory Medicine

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