Understanding and managing biotin interference in immunoassays

Abstract

Understanding and managing biotin interference in immunoassays Objectives: Biotin is a water-soluble vitamin that is an essential coenzyme in the transfer of carboxyl groups by several carboxylases involved in the synthesis of fatty acids, gluconeogenesis, amino acid metabolism, and the citric acid cycle. In the last decade or so, several reports have highlighted biotin interference causing clinically incompatible immunoassay test results. The underlying reason for this relatively new issue of biotin interference is thought to be related to the widespread use of high-dose biotin, which has led to the potential for biotin interference in routine immunoassays that use a biotin-streptavidin interaction. In November 2017 and November 2019, the US Food and Drug Administration warned the public, healthcare providers, laboratory personnel, and kit manufacturers about biotin interference and its importance. Awareness of biotin interference among laboratory staff and clinicians can prevent misdiagnosis and inappropriate treatment. The vulnerability of an immunoassay test to biotin interference is not constant; the test results may be incorrectly high or low, depending on the assay technology. Biotin can be a challenging source of interference and analytic error in terms of detection and prevention. Laboratory staff should be informed about this potential interference in immunoassays using biotin-streptavidin linkage. To reduce the likelihood of erroneous results, particular attention must be given to the test results of certain patients (e.g., patients with multiple sclerosis) or those that are not compatible with the clinical findings. To mitigate this patient safety risk, laboratories using methods vulnerable to biotin interference should develop appropriate solutions to detect and overcome biotin interference.

An Analysis of the Biotin–(Strept)avidin System in Immunoassays: Interference and Mitigation Strategies

“…There is, however, substantial evidence proving that excess consumption of biotin contributes to false immunodiagnostic results, enough for the Food and Drug Administration (FDA) to issue a warning. In 2017, and again in 2019 [65], the FDA issued a safety report to alert the public and healthcare workers about the potential harm of ingesting high levels of biotin. The FDA recommends that healthcare providers consider biotin interference as a potential source of error if a lab test result does not match with a patient's clinical presentation [66].…”

“…The FDA recommends that healthcare providers consider biotin interference as a potential source of error if a lab test result does not match with a patient's clinical presentation [66]. Although awareness of biotin interference among laboratory staff and clinicians is heavily implemented, many patients still consume high doses of biotin [65]. It is important for consumers to understand the significance of ingesting excess biotin and the consequences it may have on their lab results to help mitigate this healthcare issue [60].…”

Determination of biotin interference in pediatric obesity related ELISA research kits

“…Since biotin is also synthesized by intestinal bacteria and taken up through food and the diet, its de ciency is rare [1,2]. However, biotin de ciency occurs in some hereditary diseases, e.g., multiple sclerosis [3,4]. Biotin doses of 5-10-20 mg and 300 mg can cause blood biotin levels of approximately 200 ng/ml-1200 ng/ml [5][6][7].…”

False positive result of human chorionic gonadotropin caused by human anti-mouse antibodies

“…the interference of biotin (used as a drug or dietary supplement) in kits based on the fixation of the immune complex to microparticles through binding of streptavidin to biotin ( 11 - 13 );…”

“…• the presence of complexes of the determined antigens with immunoglobulins (i.e., with autoantibodies), such as in the case of macroenzymes, macrotroponin, macroprolactin, or macro-human chorionic gonadotropin (hCG) (1-7); • the presence of cross-reactive substances with an antibody against the antigen to be determined, which is a component of a reagent, such as digoxin-like immunoreactive substances (8-10); • the interference of biotin (used as a drug or dietary supplement) in kits based on the fixation of the immune complex to microparticles through binding of streptavidin to biotin (11)(12)(13);…”