title: Quantitation of serum free light chains does not compensate for serum immunofixation only when screening for monoclonal gammopathies.
abstract: BACKGROUND
  Detection of plasma cell dyscrasias (PCD) requires screening of serum and urine for monoclonal proteins. Several studies have demonstrated increased sensitivity and specificity when measurement of serum free light chain (SFLC) is part of the screening protocol. In addition, omission of immunofixation (IFE) in the standard work-up that includes SFLC assay has been proposed. This study attempts to define the role of the SFLC assay in a screening strategy limited to serum only. It compares outcomes to a serum-only screening strategy that omits serum IFE.
  
  
  METHODS
  Serum from 691 patients was analysed for the presence of monoclonal protein using standard serum IFE, serum protein electrophoresis (SPE) and measurement of SFLC. Data were analysed retrospectively.
  
  
  RESULTS
  Specificity and sensitivity of abnormal SFLC-ratios for the detection of monoclonal protein using IFE were 96% and 41%, respectively. Eighteen patients with negative monospecific and Bence Jones IFE, but abnormal SFLC-ratios were identified. In most cases, this could be attributed to kidney and inflammatory disease or haematological disorders. In four cases, this resulted in further diagnostic investigation and light chain disease was later detected in two cases. Light chain disease was confirmed in one case but not confirmed in the other patient. In 14 patients, Bence Jones IFE was negative, although the concentrations of SFLC suggested the presence of monoclonal Bence Jones protein at concentrations detectable by IFE. Thus, either the anti-serum failed at detection, there was polymerisation of the free light chains or the SFLC assay overestimated protein concentrations. Simulating a work-up that included IFE only if abnormalities were detected by SPE or the SFLC assay would have resulted in 26% fewer IFEs being performed, but three patients with monoclonal proteins by IFE would have been missed.
  
  
  CONCLUSIONS
  Abnormal SFLC concentrations are neither sensitive nor specific for the detection of monoclonal proteins by IFE. Not all PCD are accompanied by excessive production of SFLC, and several other conditions, such as renal disease are associated with increased SFLC concentrations. An abnormal SFLC-ratio is a specific marker for PCD, and occurs primarily in patients with haematological disease. If renal and inflammatory diseases are excluded, this should prompt further diagnostic investigation. Screening of serum without performing an IFE as a standard procedure leads to a reduction of sensitivity when compared to screening of serum that includes IFE.
authors.affiliation: Institut für Klinische Chemie und Laboratoriumsdiagnostik, Friedrlich-Schiller University Jena, Jena, Germany. kboeer@med.uni-jena.de
authors.forename: Klas
authors.initials: K
authors.lastname: Böer
authors.forename: Thomas
authors.initials: T
authors.lastname: Deufel
mesh_terms: D000368:Aged; D001536:Bence Jones Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000032:analysis* / Q000097:blood / Q000652:urine; D007146:Immunoglobulin lambda-Chains / Q000032:analysis* / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000175:diagnosis*; D012680:Sensitivity and Specificity
chemical_list: D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D001536:Bence Jones Protein