Analytical error and interference in immunoassay: minimizing risk

Abstract

Although generally robust, immunoassays remain vulnerable to occasional analytical errors that may have serious implications for patient care. Sporadic errors that occur as a result of properties of the specimen are particularly difficult to detect. They may be due to the presence of cross-reacting substances, antianalyte antibodies or antireagent antibodies, all of which may lead to erroneously high or low results. Low results may be observed for tumour markers due to high-dose hooking in the presence of very high analyte concentrations. Erroneous results can occur unexpectedly with any specimen and there is no practical means of identifying specimens likely to cause problems in immunoassays. The possibility of interference should always be considered when results do not appear to be in accord with the clinical picture. Errors can occur in even the best-managed laboratories and their early investigation is always desirable. If there is any doubt whatsoever about a result, clinical staff should be encouraged to contact the laboratory. Investigations for possible interference that can be undertaken in most laboratories include testing for linearity on dilution, recovery experiments, treatment with heterophilic blocking tubes and confirmation using a different method. It may be desirable to consult specialist laboratories if more complex studies are necessary. Informing clinical and laboratory staff of the everpresent possibility of unexpected interference, ensuring brief clinical details are available to laboratory staff, and above all facilitating excellent communication between laboratory and clinical staff are key to minimizing the risk of clinical mismanagement due to unsuspected interference.

Recurrent Hypoglycemia from Insulin Autoimmune Syndrome

“…These antibodies, known as human anti-animal antibodies and heterophile antibodies, may bind to animal immunoglobulins in the assay and produce falsely high or low results. 1,14 A method to confirm the presence of antireagent antibodies is to treat the patient sample in question with heterophilic antibody blocking tubes; a significant difference in hormone level pre-incubation and postincubation supports the presence of anti-reagent antibodies, and helps differentiate such antibodies from anti-analyte antibodies (e.g. insulin autoantibodies).…”

“…insulin autoantibodies). 1,14 C-peptide and insulin are co-secreted from pancreatic β-cells into the portal circulation in equimolar proportions. Whereas insulin is principally cleared by the liver, C-peptide is mainly metabolized by the kidneys at a substantially slower rate, resulting in a difference in circulating half-life of 5-10 minutes versus 30-35 minutes, respectively.…”

Biotina e interferenze nei metodi immunologici; problemi e opportunità

“…A fronte di questi progressi si sono palesati dei limiti per quanto riguarda l'accuratezza e la specificità, legati non solo alla difficoltà di mettere a punto anticorpi in grado di rilevare la porzione biologicamente attiva della molecola (che non sempre corrispondeva a quella immunologicamente attiva), ma anche alla dimostrazione di un numero crescente di interferenze. Esiste ormai una ricca letteratura sulle interferenze (in sostanza ogni effetto di una sostanza presente nel campione che altera il corretto valore del risultato) [10,[13][14][15]. Nel corso degli anni è stato segnalato più volte anche dalla stampa "laica" il pericolo costituito dall'assunzione di sostanze diverse come farmaci e integratori alimentari che possono interferire nei risultati degli esami misurati con metodi immunometrici.…”

The CCLM contribution to improvements in quality and patient safety

“…A relatively high frequency of analytical error has been reported for immunoassays, with associated adverse clinical outcomes. Interferences from heterophilic and antihuman antibodies still cause grossly erroneous results and adverse clinical outcomes [12][13][14][15]. Recently, data collected on the interference of paraproteins in several laboratory assays, including glucose, bilirubin, C-reactive protein, creatinine and albumin, demonstrate that the frequency of this type of error is variable and largely underreported [16,17].…”