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Analytical Performance and Diagnostic Potential of Immunoassays Determining Intact Immunoglobulin κ/λ Ratios in Monoclonal Gammopathies by Jacqueline Eckold, Wolfram Poenisch, Tim Drogies, Juergen Kratzsch, Daniel Teupser, Joachim Thiery, Mathias Bruegel

Background: HevyliteTM chain (HLC) assays with specificity for epitopes at the junction between heavy and light chains of intact immunoglobulins (Ig) allow quantification of Ig κ/λ ratios of the three major Ig classes. Calculated Ig κ/λ ratios outside the reference range indicate a monoclonal background. The primary aim of the present study was to analytically validate HLC assays and to investigate their diagnostic potential in relation to immunofixation electrophoresis (IFE) as the standard method for identification of monoclonal proteins (MPs). A second aim was to investigate the diagnostic potential of HLC assays in disease monitoring.
Methods: Precision, linearity, accuracy, sensitivity, and specificity of HLC assays for Ig classes A, G, and M were determined as parameters of analytical performance. The diagnostic performance of HLC assays in the detection of MPs was investigated in patient sera revealing monoclonal bands in IFE (n = 156). The utility of the assays in disease monitoring was investigated in a proof of principal approach by quantification of HLC ratios in subsequent sera from stem cell transplanted (ScTx) myeloma patients (n = 4).
Results: All six HLC assays revealed analytical performances suitable for application in routine diagnostics. With regard to diagnostic performance, all samples with IgA MPs in IFE (n = 54) could be identified in the HLC IgA assay. Of sera showing IgG MP in IFE (n = 69), 57 could be identified in the HLC IgG assay, whereas 12 had normal IgG κ/λ ratios. Of sera showing IgM MP in IFE (n = 26), 25 could be identified in the HLC IgM assay, 1 serum revealed a normal IgM κ/λ ratio. ScTx patients achieving IFE-negative remission had normal HLC ratios. Those who failed to achieve IFE-negative remission showed normalization of conventional monitoring parameters but revealed HLC ratios never reaching reference range.
Conclusions: HLC assays exhibit analytical performances suitable for clinical routine application. Our preliminary data from ScTx patients suggest a diagnostic potential especially of HLC IgA assay in disease monitoring. Other than that, combined application of HLC assays does not represent an alternative to IFE in first line diagnostics, in particular due to the limited diagnostic performance of the HLC IgG assay.

DOI: 10.7754/Clin.Lab.2013.131010