In response to Parussini's comments on our article,[1, 2] we regret that Theradiag Innovation and Biotherapies cannot support the results and formally contests the conclusion of our article. In their letter, it is stated that the published results are not consistent and they suspect an issue occurring during the pre-analytical process of the samples. To select the best test for clinical practice, the UMCG performed the tests with the LISA tracker and took part in a round robin experiment together with Sanquin Diagnostics and the Laboratory for Pharmaceutical Biology as mentioned in the paper. The test was performed according the manufacturer's protocol by a technician of the UMCG, who was instructed by the manufacturer. Apart from the eight presumed false-positive samples, all the other results were consistent with the other assays; therefore, a bad compliance of the product protocol appears to be unlikely. To improve their test and not to dispute the results, Theradiag received eight samples (seven clinical samples, one QC sample) from our study stated as false-positive infliximab (IFX) levels. Three of eight samples that were retested at Theradiag were still false-positive. These tests were not performed in a blinded way in contrast to the set-up of the initial round robin experiment.
Furthermore, there appear to be some inaccuracies in the graph depicted in the letter of Parussini as UMCG found levels up to 2.2 mg/L (not 5 mg/L as Theradiag erroneously mentioned) (Table 1).
|IFX level performed at UMCG, Groningen||IFX level performed at UMCG, Groningen (interpreted by Theradiag)||IFX level performed by Theradiag (bmd)|
The LISA tracker uses nonspecific anti-human IgG as a detecting antibody, which can cause false-positive results due to aspecific binding of serum proteins. Referring to the 22 extra samples recently measured by Theradiag and the Laboratory for Pharmaceutical Biology, the infliximab results obtained by Theradiag were now consistently lower and one sample was now even false-negative.
The LISA tracker is used in several publications and journals, but they never performed a study to determine the correlation between different assays for measuring IFX levels.