Negative interference from immunoglobulin M paraproteinaemia on the Roche enzymatic creatinine method

Abstract

Although enzymatic creatinine methods are subject to fewer interferences than traditional Jaffe creatinine methods, every method in clinical chemistry has limitations. We report, for the first time in the literature, a case of an immunoglobulin M (IgM) paraproteinaemia causing an undetectably low creatinine result on the Roche enzymatic assay. This interference did not occur with other enzymatic creatinine methods produced by Abbott and Siemens or the Roche Jaffe, VITROS dry slide and liquid chromatography with tandem mass spectrometry (LC-MS/MS) creatinine methods. IgM interference was confirmed as patient serum precipitated with polyethylene glycol (PEG) and anti-IgM antiserum yielded detectable Roche enzymatic creatinine results comparable to unaffected methods. The patient’s serum formed an obvious precipitate when mixed with reagent one of the Roche enzymatic creatinine method. This is in contrast to a report of positive interference from IgM paraproteinaemia in a different enzymatic creatinine method, which showed that a precipitate formed when mixing blood with reagent two. As each patient’s paraprotein has a unique structure, it is possible that there are variations in the chemical characteristics of IgM paraproteins between patients. This, as well as IgM-class antibodies’ tendency to form multimers and aggregates, can lead to unpredictable assay interferences and precipitation tendencies between different manufacturers of enzymatic creatinine reagents and their incubation steps. This case highlights the importance of continuing to question and investigates results that do not fit the clinical picture, especially as more laboratories switch from primarily using traditional Jaffe creatinine methods to enzymatic creatinine methods.

Artefactually low creatinine by Beckman Coulter enzymatic method due to immunoglobulin M paraprotein interference

“…One case of negative interference has been described with two IgM kappa paraproteins on a Mindray BS-360e platform, 7 while another case has been described with IgM kappa paraprotein on a Roche enzymatic creatinine method. 8…”

“…In the case of the Roche enzymatic creatinine interference, precipitation was reportedly visible when R1 was mixed with the patient sample, consistent with the reaction curves. 8…”

“…In contrast, a previously reported case demonstrated IgM paraprotein interference with Roche enzymatic creatinine but did not have any interference with enzymatic creatinine on Abbott, Siemens ADVIA or VITROS platforms. 8 Whilst the Abbott, Siemens, Roche and Beckman Coulter enzymatic creatinine assays have similar design, minor differences in pH, preservatives or concentrations of reagents may lead to IgM precipitation in one reagent and not other reagents. 9,10 Our retrospective review indicates that this was an isolated and likely rare event which was not seen in other patients with elevated IgM seen in our laboratory.…”

Spurious laboratory results associated with immunoglobulin M gammopathy in a dog with multiple myeloma

“…describing PEG precipitation to minimize or reduce paraprotein interference, 43 and studies have assessed PEG precipitation for multiple chemistry analytes, including creatinine 44 and phosphate 13 in human medicine, and could also be considered in veterinary medicine.…”

“…Polyethylene glycol (PEG) is a polymer of ethylene glycol that precipitates proteins by steric hindrance without denaturing or interfering with them 13 . Protocols have been published describing PEG precipitation to minimize or reduce paraprotein interference, 43 and studies have assessed PEG precipitation for multiple chemistry analytes, including creatinine 44 and phosphate 13 in human medicine, and could also be considered in veterinary medicine. Use of a different analytical method (eg, dry chemistry) could also be used, which eliminates the effects of large molecules such as paraproteins.…”