Human heterophilic antibodies display specificity for murine IgG subclasses

Bjerner, Johan; Olsen, Kari Hauge; Børmer, Ole P.; Nustad, Kjell

doi:10.1016/j.clinbiochem.2005.02.008

Cited by 30 publications

(19 citation statements)

References 24 publications

(26 reference statements)

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“…Following additional washing, the assays were developed using europium-labeled tracer antibodies. Methodological details are given in a supplemental file (web only) and in Bjerner et al (19).…”

Section: Characterization Of Heterophilic Antibodiesmentioning

confidence: 99%

Heterophilic antibody interference in commercial immunoassays; a screening study using paired native and pre-blocked sera

Bolstad

Warren

Bjerner³

et al. 2011

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: Heterophilic antibodies are still an important source of interference in immunoassays. We have conducted a screening study for interference in a panel of commercially available assays using two sera known to contain high titer Fc-reactive heterophilic antibodies. Methods: The sera were distributed to laboratories participating in the Nordic External Quality Assessment cooperation (EQANord). Duplicate samples pre-blocked with aggregated murine monoclonal MAK33 were also supplied. Discrepancies ()50%) between the results for native and blocked samples were used to classify the tested assays as susceptible to interference. A total of 170 different assay kits covering 91 analytes were tested. Results: We found that 21 assays, covering 19 different analytes, were susceptible to interference from the heterophilic antibodies in the two sera. Many of these are clinically and commercially important assays. Some of the false results were grossly elevated and could have been detrimental to patient care in a clinical setting. Conclusions: Heterophilic antibodies with Fc-reactivity remain a threat. A more widespread use of antibody fragments and aggregated immunoglobulin could potentially improve the heterophilic antibody resistance of assays intended for clinical use.

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Section: Characterization Of Heterophilic Antibodiesmentioning

confidence: 99%

Heterophilic antibody interference in commercial immunoassays; a screening study using paired native and pre-blocked sera

Bolstad

Warren

Bjerner³

et al. 2011

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Heterophilic antibodies of the IgM class dominate as interfering agents in immunochemical methods, and heterophilic antibodies of IgG and IgA classes occur mostly together with the IgM class (43). The magnitude of the effect depends on the concentration and/or titer of the interfering heterophilic antibodies, but not necessarily in a directly proportional way.…”

Section: Heterophilic Antibodies Versus Assay Reagent Antibodiesmentioning

confidence: 99%

“…Despite the initial very enthusiastic opinions on the value of these methods for the measurement of many substances of endogenous and exogenous origin, it came out that the assays using mouse monoclonal antibodies, with both simultaneous and two-step addition of capture and detection assay antibodies, are susceptible to heterophilic interference like the assays using polyclonal antibodies (43,44). Despite the initial very enthusiastic opinions on the value of these methods for the measurement of many substances of endogenous and exogenous origin, it came out that the assays using mouse monoclonal antibodies, with both simultaneous and two-step addition of capture and detection assay antibodies, are susceptible to heterophilic interference like the assays using polyclonal antibodies (43,44).…”

Section: Interference From Heterophilic Antibodies In Noncompetitive mentioning

confidence: 99%

7 Immunoassay interference – How to recognize, eliminate, or reduce it

Sztefko¹

2011

Immunodiagnostics and Patient Safety

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“…-Drug-specific interfering factors: Endogenous proteins or other substances found in naïve biological fluids specifically binding to the drug, for example, soluble multimeric drug target, proteins binding to the drug based on its mode of action, etc. -Non-specific interferants: Rheumatoid factors (RF) and other heterophilic antibodies with a potential to interact with either the drug or the assay reagent components (e.g., human anti-animal antibodies (23,24)). …”

Section: Nature and Characterization Of Pre-existing Reactivity In Admentioning

confidence: 99%

Pre-existing Antibody: Biotherapeutic Modality-Based Review

Gorovits

Clements-Egan

Birchler

et al. 2016

AAPS J

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Abstract. Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naïve subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodies vary from an adverse effect on patient safety to no impact at all and remain highly dependent on the biotherapeutic drug modality and therapeutic indication. As such, pre-existing antibodies are viewed as an immunogenicity risk factor requiring a careful evaluation. Herein, the relationships between biotherapeutic modalities to the nature, prevalence, and clinical consequences of pre-existing antibodies are reviewed. Initial evidence for pre-existing antibody is often identified during anti-drug antibody (ADA) assay development. Other interfering factors known to cause false ADA positive signal, including circulating multimeric drug target, rheumatoid factors, and heterophilic antibodies, are discussed.

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Human heterophilic antibodies display specificity for murine IgG subclasses

Cited by 30 publications

References 24 publications

Heterophilic antibody interference in commercial immunoassays; a screening study using paired native and pre-blocked sera

Heterophilic antibody interference in commercial immunoassays; a screening study using paired native and pre-blocked sera

7 Immunoassay interference – How to recognize, eliminate, or reduce it

Pre-existing Antibody: Biotherapeutic Modality-Based Review

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