A comparison between high resolution serum protein electrophoresis and screening immunofixation for the detection of monoclonal gammopathies in serum.

BACKGROUND: There are a variety of initial laboratory tests or combinations of tests that can be performed when a monoclonal gammopathy is suspected including serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum immunofixation (IFE) and serum free light chain assays. Some groups have recently used simplified "screening" IFE methods for the detection of monoclonal gammopathies leveraging the greater sensitivity of IFE over SPEP alone to improve the detection of monoclonal gammopathies. These screening techniques have been predominantly evaluated against lower resolution agarose gel electrophoresis techniques. METHODS: In this study we evaluated the diagnostic performance of the combined κ and λ light chain screening immunofixation (CLIF) in comparison to serum protein electrophoresis on a high-resolution (Sebia Hydragel 15 HR) agarose gel system. Each gel was interpreted by three adjudicators. A total of 156 patient samples were analysed. Adjudicated diagnoses based on the screening techniques were compared against the results of high resolution serum protein electrophoresis and high resolution standard immunofixation performed during routine laboratory operation. Where standard immunofixation was not performed a combination of a review of medical records, serum free light chains, UPEP and bone marrow aspirate and trephine and subsequent standard immunofixation and protein electrophoresis results where available were used to confirm the absence of a monoclonal gammopathy. RESULTS: In this cohort a total of 65 (41%) patients had a paraprotein confirmed by standard immunofixation. HR SPEP had a sensitivity and specificity of 95% and 85%, respectively, while CLIF had a sensitivity and specificity of 88% and 97%, respectively. CONCLUSIONS: Overall we found that high-resolution gel serum protein electrophoresis using a Sebia Hydragel 15 HR system was more sensitive than a screening immunofixation method (CLIF) for the detection of paraproteins in patient serum in this patient cohort. The drawback of the greater sensitivity of HR SPEP was a higher false positive rate requiring an increased utilisation of follow up immunofixation electrophoresis.

Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint.

Monoclonal gammopathies are characterised by the production of a monoclonal immunoglobulin or free light chains by an abnormal plasma cell or B-cell clone and may indicate malignancy or a precursor (MGUS). There is currently no consensus on the initial test or combination of tests to be performed in suspected monoclonal gammopathies but serum protein electrophoresis and urine protein electrophoresis are commonly requested as initial investigations. If abnormal, immunofixation electrophoresis is then performed to confirm the presence of paraprotein and to determine its heavy and light chain type. Recently, some groups have developed simplified "screening" IFE methods for use in parallel to SPEP for the detection monoclonal gammopathies. We argue here that screening IFE may be of benefit in clinical laboratories using SPEP with poor resolution in the ß-region, assisting in the detection of mainly IgA paraprotein, but may be of less benefit in laboratories utilising higher resolution gels. Further it may increase the detection of trace bands of questionable clinical significance, representing transient phenomena in infectious and auto-immune conditions or very low risk MGUS. The increased detection of these bands using screening IFE would require further patient follow up, possibly causing unnecessary patient anxiety and additional follow up healthcare costs.

Myocardial endothelin-1 release and indices of inflammation during angioplasty for acute myocardial infarction and stable coronary artery disease.

BACKGROUND: Elevations in endothelin-1 (ET-1) and inflammatory cytokines may impair myocardial reperfusion through the induction of microvascular constriction or obstruction; however, the generation of these factors close to the site of lesion rupture is unknown. METHODS AND RESULTS: Coronary sinus (CS) and aortic blood was sampled during angioplasty for acute myocardial infarction (AMI) or stable angina to assess the local release of ET-1, interleukin-1beta, interleukin-6, tumor necrosis factor-alpha and C-reactive protein following atherosclerotic plaque rupture. Transthoracic echocardiography documented left ventricular function in AMI. ET-1 levels were higher in CS than in aortic blood in AMI (3.0 +/- 0.3 pmol/L vs 2.6 +/- 0.3 pmol/L, P =.04), but not in stable angina (1.7 +/- 0.2 pmol/L vs 1.5 +/- 0.3 pmol/L, P = NS). CS ET-1 levels were also higher in AMI than in stable angina (3.0 +/- 0.3 pmol/L vs 1.7 +/- 0.2 pmol/L, P =.002), and correlated with left ventricular dysfunction (R(2) = 0.51, P =.02). In contrast, C-reactive protein levels were higher in CS than in aortic blood only in stable angina (2.3 +/- 0.4 mg/L vs 1.8 +/- 0.3 mg/L, P =.01). Similarly, CS tumor necrosis factor-alpha was higher in stable angina than in AMI (6.0 +/- 1.4 pg/mL vs 2.5 +/- 0.9 pg/mL, P =.02). CONCLUSIONS: Local myocardial release of ET-1 is highest in AMI, where it relates to the extent of myocardial dysfunction. Although local inflammation is a component of stable coronary artery disease, it does not appear acutely enhanced in AMI.