Lack of observed interference by therapeutic monoclonal antibodies in select commonly utilized immunoassays

Kornelia D Galior; Paula M Ladwig; Melissa R Snyder; Alicia Algeciras-Schimnich; Joshua A Bornhorst; Darci R Block; Nikola A Baumann; Maria Alice V Willrich

doi:10.1016/j.clinbiochem.2023.110685

Lack of observed interference by therapeutic monoclonal antibodies in select commonly utilized immunoassays

Clin Biochem. 2023 Nov:121-122:110685. doi: 10.1016/j.clinbiochem.2023.110685. Epub 2023 Nov 14.

Authors

Kornelia D Galior¹, Paula M Ladwig², Melissa R Snyder², Alicia Algeciras-Schimnich², Joshua A Bornhorst², Darci R Block², Nikola A Baumann², Maria Alice V Willrich³

Affiliations

¹ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA. Electronic address: kgalior@emory.edu.
² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
³ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Electronic address: willrich.mariaalice@mayo.edu.

PMID: 37972806
DOI: 10.1016/j.clinbiochem.2023.110685

Abstract

Background: Therapeutic monoclonal antibodies (tmabs) have been hypothesized to interfere with immunoassay measurements, although studies investigating this potential new class of interference are lacking. This study evaluated the effects of tmabs used in cancers ipilimumab (Bristol Myers Squibb), nivolumab (Bristol Myers Squibb), pembrolizumab (Merck) and autoimmune disorders adalimumab (AbbVie), infliximab (Janssen) and vedolizumab (Takeda) in common immunoassays used in the clinical laboratory.

Methods: Residual sera from 10 randomly chosen patients were split into two tubes and spiked with same volume (approximately 5 % final volume) of either saline (control) or 6 tmabs (final concentration of 100 μg/mL each). Concentrations from sixteen analytes in 19 different assays were assessed: TSH (Roche and Beckman), free thyroxine (Roche and Siemens), cortisol (Beckman), Cancer Antigens (CA): CA19-9 (Beckman), CA15-3 (Roche), CA125 (Roche), and CA27.29 (Siemens), carcinoembryonic antigen (Beckman), alpha-fetoprotein (Beckman), thyroglobulin (Beckman) and thyroglobulin antibodies (Beckman), thyroid peroxidase antibody (Beckman), beta-human chorionic gonadotropin (Roche and Beckman), total prostate-specific antigen (Roche), parathyroid hormone (Roche) and antinuclear antibodies IgG (Werfen). The tmab spiked residual sera were compared with matched saline spiked sera and percent error was assessed against allowable total error defined from biological variation or CLIA limits.

Results: None of the tested immunoassays were affected by the presence of the tmabs, in samples within or outside assay reference intervals. The median % error among all immunoassays ranged between -2.0% (for TSH) to 2.7% (for TPO Ab assay).

Conclusion: These findings demonstrate no detectable tmab interference for the assessed immunoassays using spiked preparations of the tmabs in residual human sera. The findings are limited to the tmabs and immunoassays studied here.

Keywords: Heterophile antibodies; Immunoassays; Interferences; Laboratory tests; Monoclonal antibody therapies.

MeSH terms

Antibodies, Monoclonal*
Autoimmune Diseases*
Humans
Immunoassay
Male
Thyroglobulin
Thyrotropin

Substances

Antibodies, Monoclonal
Thyroglobulin
Thyrotropin