Endocrine Abstracts

Asfotase alfa (AA, STRENSIQ, Alexion Pharmaceuticals, Inc.) is the first FDA-Approved treatment for patients with hypophosphatasia, the result of a mutation in the tissue-nonspecific alkaline phosphatase (ALPL) gene. Because it contains the ALP active site, AA is able to catalyse the substrate as the antibody-conjugated ALP would within an assay. Therefore, AA present in a patient’s sample may generate a false positive or a false negative result. We investigated whether the presence of AA within a sample induces interference in measurements of LH, TSH, FSH and fT4 in large automated analysers (Siemens Immulite and ADVIA Centaur, Roche Diagnostics COBAS 6000 and Abbott Architect) using ALP as detection system or an alternate detection system. AA was added to samples at concentrations from 0.08–5 μg/ml. All experiments were repeated a minimum of 3 times. The presence of AA was demonstrated in ALP chemistry assay (COBAS and Centaur) by measuring the activity of the enzyme. ALP showed a significant (ANOVA, P<0.0001) linear increase in concentration with increasing asfotase alfa concentrations. We showed no effect of AA in assays using ruthenium (COBAS and Centaur fT4, COBAS TSH), acridium ester (Centaur and Architect LH, Centaur TSH and Architect FSH), nor ALP (Immulite LH and FHS). Although we were not able to show an effect of AA on the assay we tested, demonstrating the high specificity of the detection antibodies in this instance, an interference cannot be ruled out for all assays that uses ALP. The likelihood of misdiagnosis remains low but cannot be excluded and consultants should ensure laboratories are aware of the presence of AA in the sample sent for analysis. The presence of AA must be taken into consideration when analysing blood samples using certain assay technology to avoid any risk of misinterpretation of false positive/negative results.