title: [Analysis of the relationship of heavy/light chain pairs of immunoglobulin (Hevylite) to the results of gel electrophoresis and nefelometric examination of serum proteins at the time of multiple myeloma diagnosis].
abstract: BACKGROUND
  The diagnostics and treatment of multiple myeloma (MM) requires precise analysis of serum immunoglobulins, which might be limited by the sensitivity of standard examination methods. Hevylite method enables quantitative analysis of heavy/light chain pairs (HLC) of normal and tumor IgG and IgA immunoglobulin and their ratio (HLC-r). The aim of the study was to assess the contribution of Hevylite method in the diagnostics of MM in comparison with nephelometry (NEF), standard protein electrophoresis (SPE), immunofixation electrophoresis (IFE) and the examination of serum free light chains (FLC) of immunoglobulin using Freelite test and heavy/light chain pairs of immunoglobulin (HLC) using Hevylite.
  
  
  METHODS
  Using the methods Hevylite, NEF, SPE, IFE and Freelite, we examined a cohort of 134 individuals fulfilling the International Myeloma Working Group (IMWG) criteria. 96 patients were of IgG and 38 of IgA type.
  
  
  RESULTS
  The levels of HLC-kappa (K) and HLC-lambda (L), as well as HLC-r were independent of age and gender. Abnormal HLC levels were present in 84-100%, pathological HLC-r was in 92-100% cases based on MIg isotype. We found strong positive correlation between IgG and IgA (NEF) and the sum of HLC IgG-K + IgG-L (Hevylite) (r = 0.80, p < 0.0001) and HLC IgA-K + IgA-L (r = 0.75, p < 0.0001). Very strong positive correlation was between the concentration of MIg (SPE) and the levels of HLC (Hevylite) in IgG-K (r = 0.73), IgG-L (r = 0.76), IgA-K (r = 0.70) and IgA-L (r = 0.89), p < 0,0001. Systematic difference between Hevylite vs. MIg (SPE) was confirmed by Bland-Altmann test in the case of HLC IgA-K and IgA-L (not HLC IgG-K and IgG-L), and in the correlation of HLC with IgG and IgA (NEF). The most significant correlation between SPE (patients with < 15 g/L) vs. Hevylite was found within the analysis of HLC IgG-K+ IgA-K (r = 0.85, p < 0.0001), and in the whole cohort of MM patients, i.e. IgG + IgA-kappa and lambda (r = 0.76, p < 0.0001), confirmed by Bland-Altmann test. Tight positive correlation was between HLC-r and index of monoclonality FLC-K/L in MM of IgG and IgA type MM (p < 0.0001).
  
  
  CONCLUSIONS
  Hevylite method, especially the assessment of HLC-r of IgA type MM is more sensitive in comparison with SPE evaluated by NEF, and increases the diagnostic sensitivity and the extent of tumor mass examination. Despite its limitation in the case of high levels of IgG type MIg, Hevylite technique has a promising potential to enrich the standard analytic tools as it enables to assess the concentration and ratio of the levels of both tumor and physiological immunoglobulins e.g. depth of immunoparesis, valid especially in MM with low levels of MIg.
authors.forename: Vlastimil
authors.initials: V
authors.lastname: Ščudla
authors.forename: Pavel
authors.initials: P
authors.lastname: Lochman
authors.forename: Tomáš
authors.initials: T
authors.lastname: Pika
authors.forename: Jana
authors.initials: J
authors.lastname: Zapletalová
authors.forename: Jiří
authors.initials: J
authors.lastname: Minařík
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Bačovský
mesh_terms: D000328:Adult; D001797:Blood Protein Electrophoresis; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007143:Immunoglobulin Heavy Chains / Q000097:blood*; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D007146:Immunoglobulin lambda-Chains / Q000097:blood; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000276:immunology*; D009391:Nephelometry and Turbidimetry; D011237:Predictive Value of Tests
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains
keywords: multiple myeloma - monoclonal immunoglobulin - levels of light/heavy chain pairs of immunoglobulin - HLC-kappa/HLC-lambda ratio - Hevylite - serum protein electrophoresis - immunofixation electrophoresis - free light chains of immunoglobulin - Freelite.