TL;DR: Owing to the unique properties of each M-protein, it is impossible to protect common clinical chemistry test systems completely from gammopathy interference and efficient ways for the detection of such interference are needed.
Abstract: Monoclonal gammopathy is characterized by the presence of an M-protein in serum or urine that has homogeneous structural and functional properties. It can occur in very high concentrations and may cause significant interference in clinical chemistry assays. Examples of gammopathy interference for the analytes glucose, bilirubin, gamma-glutamyltransferase, urea and ferritin are presented. Various mechanisms of interference are described, such as the production of turbidity by the M-protein and the binding of the M-protein to a component of the test system or analyte. In immunoglobulin tests, the M-protein is the analyte itself and may not be completely bound by the test antibody owing to its structural properties. Modern analyzers can detect unusual changes in absorption during the course of a reaction, and thus the formation of turbidity due to M-proteins. This interference may be prevented by optimizing the buffering conditions of the reagents to avoid the formation of turbidity or by removal of the M-protein prior to analysis of the sample. Owing to the unique properties of each M-protein, it is impossible to protect common clinical chemistry test systems completely from gammopathy interference. Therefore, efficient ways for the detection of such interference are needed.
TL;DR: It does not seem possible to predict which samples will cause interference in the measurement of inorganic phosphate using an unmodified acid/molybdate assay but it is important that the clinical implications of this problem are appreciated.
Abstract: The measurement of inorganic phosphate using an unmodified acid/molybdate assay is known to be subject to interference when paraproteinaemia exists. This phenomenon, due to precipitation in the reaction mixture, is not common to all paraproteins. We studied sera from 35 patients to determine whether interference in the assay was related to particular electrophysical characteristics of the paraproteins. There were spuriously elevated phosphate concentrations in 48.6% of the sera assayed. This could not be related to a direct effect of light chain type, electrical charge or IgG subclass. No IgA paraproteins were found to cause interference but there were immunoglobulin G (IgG) and immunoglobulin M (IgM) paraproteins in both the 'interfering' and 'non-interfering' groups. The median paraprotein concentration was similar in both groups but, where interference occurred, the degree increased in line with the paraprotein concentration. Although it does not seem possible to predict which samples will cause interference, it is important that the clinical implications of this problem are appreciated.
TL;DR: I compared seven buffers and four chromogens for determining serum iron, to evaluate the frequency of falsely high or low concentrations of iron in 59 sera containing monoclonal immunoglobulins, finding that the problem cannot be solved by a simple two- or threefold dilution of the sample.
Abstract: I compared seven buffers and four chromogens for determining serum iron, to evaluate the frequency of falsely high or low concentrations of iron in 59 sera containing monoclonal immunoglobulins. The results for these direct assays with untreated sera were compared with those obtained by a proposed reference method (Br J Haematol 1978;38:291-4) with protein-free filtrates of the same sera. Sera with monoclonal immunoglobulins sometimes yielded erroneous results; the frequency of errors, which could be as much as 29% (17/59), depended on the composition of buffer and color reagent. Addition of thiourea or a detergent (Triton X-405) to some of the buffers lowered the frequency of errors, but did not abolish them. In only a few of the investigated buffer/chromogen combinations were no errors found. Detection of errors by analyzing the absorbance pattern after mixing sample and buffer was not always successful. Moreover, the presence and magnitude of errors bore no relationship to the type or the concentration of the monoclonal immunoglobulins. Unfortunately, the problem cannot be solved by a simple two- or threefold dilution of the sample.
TL;DR: The Technical Brief described an artificially increased total bilirubin in a patient with a monoclonal IgM paraprotein as rare, but 6 patients at 2 hospitals with documented paraproteins who had falsely increased serum total bilIRubin are identified.
Abstract: We read with interest the Technical Brief by Smogorzewska et al. (1) describing an artificially increased total bilirubin in a patient with a monoclonal IgM paraprotein. Monoclonal paraproteins have been shown to artifactually influence several automated assays of different methodologies, including nephelometry, turbidometry, and immunologic assays, by forming precipitates during the assay procedure (2)(3)(4)(5)(6)(7). The total bilirubin assay on the Hitachi 917 automatic chemistry analyzer (Roche Diagnostics) has been reported to yield falsely increased bilirubin values as a result of paraprotein interference (1)(8). Smogorzewska et al. (1) and Pantanowitz et al. (8) described this artifact as rare, but we have identified 6 patients at 2 hospitals with documented paraproteins who had falsely increased serum total bilirubin. Notably, patients with artifactually high total …
TL;DR: To clarify the inconsistent results of markedly elevated serum creatinine together with serum urea in the lower normal range and no symptoms of renal disease, creat inine was also determined by the Jaffé method and by HPLC.
Abstract: Accessible online at: www.karger.com/journals/nef Dear Sir, We report 3 patients with false elevated plasma creatinine concentration due to interference of monoclonal IgM in a routine enzymatic test for creatinine determination (Roche Diagnostics). The true plasma creatinine as determined by HPLC was in the reference range for all patients. One patient, a 60-year-old man, had been seen as an outpatient for Waldenström’s macroglobinemia (WM) that had been diagnosed 6 years earlier. Since he developed pancytopenia due to diffuse lymphoma infiltration of the bone marrow, chemotherapy was started 4 months earlier. The regimen included mitoxantrone, chlorambucil and prednisolone. The lymphoma remitted as determined by bone marrow biopsy. However, monoclonal IgM serum levels increased from 5.9 up to 20.7 g/l during this time. Simultaneously, serum creatinine rose from 1.5 to 5.4 mg/dl. Renal involvement in the course of the WM was suggested. He was admitted with suspected chronic renal failure in April 1999. Physical examination was normal. Routine blood tests showed an erythrocyte sedimentation rate of 100 mm/1st hour and leukopenia of 2,500/Ìl with normal white blood cell differential count. Except for elevated creatinine, other blood tests, including serum urea and uric acid, were within the respective reference ranges. Urine tests showed no proteinuria or active sediment that would indicate renal amyloidosis or IgM deposits on the basal membrane. Serum viscosity was slightly raised to 1.38 mPa (normal range 1.1–1.3), as was total serum protein with 8.2 g/dl. Cryoglobulins were not detected. Serology for autoantibodies was negative. By ultrasound, kidneys were normal in size and structure. To clarify the inconsistent results of markedly elevated serum creatinine together with serum urea in the lower normal range and no symptoms of renal disease, creatinine was also determined by the Jaffé method and by HPLC. The Jaffé method yielded a value of 1.3 mg/dl and HPLC a valTable 1. Different plasma creatinine concentrations showing the presence of interference with the enzymatic creatinine method