Commutability of cytomegalovirus WHO international standard in different matrices

Abstract

Commutability of quantitative standards allows patient results to be compared across molecular diagnostic methods and laboratories. This is critical to establishing quantitative thresholds for use in clinical decision-making. A matrix effect associated with the 1st cytomegalovirus (CMV)WHOinternational standard (IS) was identified using the Abbott RealTime CMV assay. A commutability study was performed to compare the CMVWHOIS and patient specimens diluted in plasma and whole blood. Patient specimens showed similar CMV DNA quantitation values regardless of the diluent or extraction procedure used. The CMV WHOIS, on the other hand, exhibited a matrix effect. The CMV concentration reported for theWHOIS diluted in plasma was within the 95% prediction interval established with patient samples. In contrast, the reported DNA concentration of the CMV WHOIS diluted in whole blood was reduced approximately 0.4 log copies/ml, and values fell outside the 95% prediction interval. Calibrating the assay by using the CMVWHOIS diluted in whole blood would introduce a bias for CMV whole-blood quantitation; samples would be reported as having higher measured concentrations, by approximately 0.4 log IU/ml. Based on the commutability study with patient samples, the RealTime CMV assay was standardized based on the CMVWHOIS diluted in plasma. A revision of the instructions for use of the CMVWHOIS should be considered to alert users of the potential impact from the diluent matrix. The identification of a matrix effect with the CMVWHOIS underscores the importance of assessing commutability of the IS in order to achieve consistent results across methods.