title: Analytical performance and diagnostic potential of immunoassays determining intact immunoglobulin kappa/lambda ratios in monoclonal gammopathies.
abstract: BACKGROUND
  Hevylite chain (HLC) assays with specificity for epitopes at the junction between heavy and light chains of intact immunoglobulins (Ig) allow quantification of Ig kappa/lambda ratios of the three major Ig classes. Calculated Ig kappa/lambda 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 kappa/lambda 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 kappa/lambda 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.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Eckold
authors.forename: Wolfram
authors.initials: W
authors.lastname: Poenisch
authors.forename: Tim
authors.initials: T
authors.lastname: Drogies
authors.forename: Juergen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Mathias
authors.initials: M
authors.lastname: Bruegel
mesh_terms: D015415:Biomarkers / Q000097:blood; D006801:Humans; D007118:Immunoassay; D007145:Immunoglobulin kappa-Chains / Q000097:blood*; D007146:Immunoglobulin lambda-Chains / Q000097:blood*; D015166:Monitoring, Immunologic / Q000379:methods*; D009101:Multiple Myeloma / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000601:surgery; D010265:Paraproteinemias / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy; D011237:Predictive Value of Tests; D012074:Remission Induction; D015203:Reproducibility of Results; D033581:Stem Cell Transplantation; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains