title: Immunoglobulin heavy/light chain analysis enhances the detection of residual disease and monitoring of multiple myeloma patients.
abstract: OBJECTIVE
  To evaluate the clinical utility of incorporating a novel heavy/light chain immunoassay (HLC) into the existing methods for the assessment of multiple myeloma (MM) patients.
  
  
  METHODS
  Convenience sera samples from 90 previously treated IgG and IgA MM patients in different disease stages were analyzed. The study was conducted in Clinical Hospital Center Zagreb between 2011 and 2013. The collected sera were analyzed by standard laboratory techniques (serum protein electrophoresis, quantification of total immunoglobulins, serum immunofixation, serum free light chain [FLC] assay) and HLC assay.
  
  
  RESULTS
  HLC ratios outside the normal range were found in 58 of 90 patients, including 28 out of 61 patients with total immunoglobulin measurements within the normal range and 5 out of 23 patients in complete response. Both elevated HLC isotype level and abnormal HLC ratio correlated with the parameters of tumor burden, including percentage of plasma cells in the bone marrow (P<0.001 and P=0.002, respectively) and an abnormal serum FLC ratio (for both P<0.001). In addition, abnormal HLC isotype level correlated with serum beta-2-microglobulin level (P=0.038). In terms of prognosis, abnormal HLC isotype level and abnormal HLC ratio were significantly associated with shorter overall survival (P<0.001 and P=0.002, respectively). Interestingly, suppression of the uninvolved (polyclonal) isotype pair, but not other non-myeloma immunoglobulin isotypes, was also associated with a shorter overall survival (P=0.021). In a multivariate analysis, an abnormal HLC ratio and β2-microglobulin level >3.5mg/L were independent risk factors for survival.
  
  
  CONCLUSIONS
  The new HLC assay has greater sensitivity in detecting monoclonal protein, correlates with tumor burden markers, and affects patients' outcome.
authors.affiliation: Josip Batinić, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia, batinic.josip@gmail.com.
authors.forename: Josip
authors.initials: J
authors.lastname: Batinić
authors.forename: Zinaida
authors.initials: Z
authors.lastname: Perić
authors.forename: Dragana
authors.initials: D
authors.lastname: Šegulja
authors.forename: James
authors.initials: J
authors.lastname: Last
authors.forename: Sanja
authors.initials: S
authors.lastname: Prijić
authors.forename: Klara
authors.initials: K
authors.lastname: Dubravčić
authors.forename: Lidija
authors.initials: L
authors.lastname: Volarić
authors.forename: Dubravka
authors.initials: D
authors.lastname: Sertić
authors.forename: Ivo
authors.initials: I
authors.lastname: Radman
authors.forename: Sandra
authors.initials: S
authors.lastname: Bašić-Kinda
authors.forename: Danica
authors.initials: D
authors.lastname: Matišić
authors.forename: Drago
authors.initials: D
authors.lastname: Batinić
authors.forename: Boris
authors.initials: B
authors.lastname: Labar
authors.forename: Damir
authors.initials: D
authors.lastname: Nemet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000097:blood* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D009194:Myeloma Proteins / Q000276:immunology; D011379:Prognosis; D012307:Risk Factors
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D009194:Myeloma Proteins; C085016:multiple myeloma M-proteins