In vitro evaluation of potential interference of lokivetmab with protein electrophoresis and immunofixation

Abstract

Objective In humans, misdiagnoses of monoclonal gammopathy after use of therapeutic monoclonal antibodies has been documented. This triggers concerns for similar misdiagnoses in animals treated with monoclonal antibodies. The aim of this study was to evaluate if lokivetmab interferes with serum protein electrophoresis and immunofixation electrophoresis in dogs.

Material and methods Residual sera from 25 client-owned, healthy blood donor dogs from 2 veterinary hospitals in Germany were used. The residual sera were analysed with serum protein electrophoresis and immunofixation electrophoresis before and after being spiked with lokivetmab at a concentration of 10 µg/ml (corresponding to the mean peak serum concentration after a subcutaneous injection of 2 mg/kg lokivetmab).

Results No monoclonal gammopathy was observed on serum protein electrophoresis and all proteins had a normal distribution pattern without any pathologic bands on immunofixation electrophoresis. The absolute γ-globulin values of spiked samples, however, were significantly higher than in the native sera although they remained within the reference interval. No other globulin fractions were significantly different.

Conclusion and clinical relevance This study suggests that lokivetmab at a dose of 2 mg/kg is not detected as a monoclonal peak on serum protein electrophoresis or immunofixation electrophoresis, and thus is unlikely to lead to a misdiagnosis of other diseases that are characterised by monoclonal gammopathies.

Zusammenfassung

Ziel Beim Menschen wurden Fehldiagnosen einer monoklonalen Gammopathie nach Verwendung therapeutischer monoklonaler Antikörper dokumentiert. Dies löst Bedenken hinsichtlich ähnlicher Fehldiagnosen bei Tieren aus, die mit monoklonalen Antikörpern behandelt wurden. Ziel dieser Studie war zu evaluieren, ob Lokivetmab mit der Serumproteinelektrophorese und der Immunfixationselektrophorese bei Hunden interferiert.

Material und Methoden Zur Untersuchung gelangten übrig gebliebene Serumproben von 25 privat gehaltenen, gesunden Blutspenderhunden aus 2 Tierkliniken in Deutschland. Die Serumproben wurden vor und nach der Mischung mit Lokivetmab in einer Konzentration von 10 µg/ml mittels Serumproteinelektrophorese und Immunfixationselektrophorese analysiert. Die gewählte Konzentration entspricht der mittleren maximalen Serumkonzentration nach einer subkutanen Injektion von 2 mg/kg Lokivetmab.

Ergebnisse Bei der Serumproteinelektrophorese zeigte sich keine monoklonale Gammopathie und bei der Immunfixationselektrophorese wiesen alle Proteine ein normales Verteilungsmuster ohne pathologische Banden auf. Die absoluten γ-Gammaglobulin-Werte der aufgestockten Proben waren jedoch signifikant höher als die der nativen Seren, blieben jedoch im Referenzintervall. Die anderen Globulinfraktionen differierten nicht signifikant.

Schlussfolgerung und klinische Relevanz Die Ergebnisse legen nahe, dass Lokivetmab in einer Dosis von 2 mg/kg nicht als monoklonaler Peak bei der Serumprotein- oder Immunfixationselektrophorese erkannt wird und daher wahrscheinlich nicht zu einem fälschlichen Verdacht einer mit einer monoklonalen Gammopathie einhergehenden Erkrankung führt.

Key words

Atopy - dog - globulins - interleukin-31 - gammopathy

Schlüsselwörter

Atopie - Hund - Globuline - Interleukin-31 - Gammopathie

*Neoklis Apostolopoulos and Athanasia Mitropoulou are joint first author.

^ID https://orcid.org/0000-0001-9749-0795

Publication History

Received: 10 November 2020

Accepted: 22 December 2020

Article published online:
23 August 2021

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