Endogenous anti-streptavidin antibodies causing erroneous laboratory results more common than anticipated

Abstract

All immunological methods are vulnerable to different kinds of interference. The purpose of this work was to study the cause and frequency of method-dependent interference in the Roche thyroid immunoassays. Serum samples with discordant thyroid function tests (TFT) were selected from samples sent to the Hormone Laboratory, Oslo University Hospital from June 2013 to September 2018. We identified 93 patients with discordant pathological TFT when analysed with the Roche methods and normal results when analysed with alternative methods. 42 of these samples were sent to Roche Diagnostics (Germany) for investigation of the interfering substance. Roche found interference to be caused by the presence of endogenous anti-streptavidin antibodies (ASA) (34 of 42 patients), ruthenium or the idiotype of the ruthenium labelled antibody (3 of 42 patients) and mouse antigens (1 of 42 patients). Method-dependent interference was estimated to affect 0.37% of the patients investigated in our laboratory. Interference due to the presence of endogenous ASA were further explored in other (non-thyroid) immunoassays by comparing analyte levels before and after pre-adsorption of the patients’ sera with streptavidin-coated paramagnetic beads. An underestimation of hormone levels was observed in sandwich immunoassays, while an overestimation was found in competitive assays. Method-dependent interference in Roche thyroid immunoassays is caused mainly by ASA and is not a very rare phenomenon. Misleading results may lead to misdiagnosis and inappropriate medical treatment. The supplier of the assay should be alerted when the available alternative methodology reveals method-dependent errors.

Keywords:

• Immunoassay
• antibody
• streptavidin
• ruthenium
• biotin

Acknowledgments

We wish to thank the method specialists, Biomedical Laboratory Scientists; Inger Svendsen, Liv Sandnes and Guro Clementz for analysing and organising the freezing of the discordant samples. We also acknowledge the collaboration with the endocrinologists at our hospital’s out-patient thyroid clinic. We, thank Kristin Lilleholt at Sørlandet Hospital who sent the first three samples with confirmed ASA to Roche Diagnostics, Roche Diagnostics for their contribution to this study and Robin Holtedahl for help with the statistics and revision of the manuscript.

Disclosure statement

LK Dahll reports lecture fee and travel expenses from Roche Diagnostics. Roche Diagnostics have had the opportunity to read and give comments on the manuscript before submission. The remaining authors report no potential conflict of interest.