A Black Swan in clinical laboratory practice: the analytical error due to interferences in immunoassay methods

Abstract

It is well known that the results of immunoassay methods can be affected by specific or non-specific interferences, ranging from 0.4% to 4.0%. The presence of interference may greatly compromise the accuracy of immunoassay analyses causing an error in the measurement, producing false-positive or false-negative results. From a clinical point of view, these analytical errors may have serious implications for patient care because they can cause misdiagnosis or inappropriate treatment. Unfortunately, it is a very difficult task to identify the irregular analytical errors related to immunoassay methods because they are not detectable by normal laboratory quality control procedures, are reproducible within the test system, may be clinically plausible and are relatively rare. The first line of defense against erroneous results is to use in laboratory practice only immunoassay systems with the highest level of robustness against interference. The second line of defense is always taking into account the possibility of interference in immunoassay results. A correct approach should be addressed on identification of samples at high risk of interference. The attainment of this goal requires a critical review of the test result in relation to patient's clinical conditions and literature data, taking into account the analytical characteristics of the immunoassay system. The experts in immunoassay systems should make every effort to find some specific and reliable quality indicators for irregular analytical errors in order to better detect and monitor erroneous immunoassay results due to specific or non-specific interferences.

HMGB1 concentration measurements in trauma patients: assessment of pre-analytical conditions and sample material

“…(Tate and Ward 2004) Cross-reactivity, unsuspected protein-protein bindings, and lipemia are all known to cause interference, and these factors can depend on type of sample material. (Tate and Ward 2004; Clerico et al 2018) In line with this, both serum and plasma components that interfere with HMGB1 detection by ELISA systems have been reported, yielding different results in serum vs. plasma depending on disease state. (Urbonaviciute et al 2007; Basso et al 2017; Lehner et al 2012) We have therefore compared HMGB1 levels measured by ELISA in simultaneously acquired serum and plasma samples from patients early after trauma.…”

“…The application of immunoassays in complex matrices such as plasma and serum is challenged by interference, (Tate and Ward 2004; Clerico et al 2018) also known as “matrix effects”. Polyreactive antibodies or unsuspected protein–protein interactions may interfere with antibody detection, decreasing both sensitivity and specificity of the assay and consequently challenging reliable HMGB1 detection in clinical samples.…”

Biphasic Release of the Alarmin High Mobility Group Box 1 Protein Early After Trauma Predicts Poor Clinical Outcome

“…(Tate and Ward 2004) Cross-reactivity, unsuspected protein-protein bindings, and lipemia are all known to cause interference, and these factors can depend on type of sample material. (Tate and Ward 2004;Clerico et al 2018) In line with this, both serum and plasma components that interfere with HMGB1 detection by ELISA systems have been reported, yielding different results in serum vs. plasma depending on disease state. We have therefore compared HMGB1 levels measured by ELISA in simultaneously acquired serum and plasma samples from patients early after trauma.…”

The Selectivity of Molecularly Imprinted Polymers

“…In the case of analytical applications, this means the comparative analysis of many different samples with the MIP method compared to a standard method. If one wishes to appreciate the difficulty of achieving real life selectivity, one needs only to read recent papers on the unreliability of the selectivity of antibodies [ 12 , 13 , 14 ].…”