RESUMEN
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.
Asunto(s)
Paraproteinemias , Espectrometría de Masas en Tándem , Cromatografía Liquida/métodos , Creatinina , Humanos , Inmunoglobulina M , Paraproteinemias/diagnóstico , ParaproteínasRESUMEN
Multiple myeloma is a haematological cancer caused by malignant plasma cells in the bone marrow that can result in organ dysfunction and death. Recent novel treatments have contributed to improved survival rates, including monoclonal antibody therapies that target the CD38 protein on the surface of plasma cells. Anti-CD38 therapies are IgG kappa monoclonal antibodies that are given in doses high enough for the drug to be visible on serum protein electrophoresis as a small paraprotein. We present a case where isatuximab, the most recent anti-CD38 monoclonal antibody to be approved for treatment of myeloma, obscured the patient's paraprotein on gel immunofixation, so that complete remission could not be demonstrated. This was resolved using the isatuximab Hydrashift assay. The interference on gel immunofixation was unexpected because isatuximab migrated in a position distinct from the patient's paraprotein on capillary zone electrophoresis. We demonstrate the surprising finding that isatuximab migrates in a different position on gel electrophoresis compared to capillary zone electrophoresis. It is vital that laboratories are aware of the possible interference on electrophoresis from anti-CD38 monoclonal antibody therapies, and are able to recognise these drugs on protein electrophoresis. The difference in isatuximab's electrophoretic mobility on capillary and gel protein electrophoresis makes this particularly challenging. Laboratories should have a strategy for alternative analyses in the event that the drugs interfere with assessment of the patient's paraprotein.