title: IgMκ and IgMλ Measurements for the Assessment of Patients with Waldenström's Macroglobulinaemia.
abstract: OBJECTIVE
  Accurate quantification of monoclonal IgM immunoglobulins is essential for response assessment in patients with Waldenström's macroglobulinaemia (WM). The propensity of IgM to form multimers in serum makes sample evaluation by current laboratory methods particularly challenging.
  
  
  METHODS
  We assessed the precision and linearity of IgMκ and IgMλ heavy/light chain (HLC, Hevylite) assays, and established reference intervals using 120 normal donor sera. We compared the quantitative performance of HLC assays with serum protein electrophoresis (SPE) and total IgM nephelometry for 78 diagnostic samples and follow-up samples from 25 patients with WM. Comparisons were made between the three methods for diagnostic sensitivity and response assessment.
  
  
  RESULTS
  IgMκ and IgMλ HLC assays showed low imprecision and good linearity. There was good agreement between summated HLC (IgMκ + IgMλ) and total IgM (measured nephelometrically; R2= 0.90), but only moderate agreement between involved IgM HLC and SPE densitometry (R2= 0.49). Analysis of 120 normal donor sera produced the following normal ranges: IgMκ: 0.29-1.82 g/L; IgMλ: 0.17-0.94 g/L; IgMκ/IgMλ ratio: 0.96-2.30. Using these ranges, IgM HLC ratios were abnormal in all WM presentation sera tested, including 15 with non-quantifiable SPE. Despite discordance in quantitation, responses assigned with HLC assays showed excellent agreement to those based on international guidelines using SPE or total IgM; although abnormal HLC ratios indicated residual disease in some patients with negative electrophoresis results.
  
  
  CONCLUSIONS
  Nephelometric assessment of IgMκ and IgMλ HLC pairs offers a quantitative alternative to traditional laboratory techniques for the measurement of monoclonal IgM and may aid in the management of WM. Clin Cancer Res; 22(20); 5152-8. ©2016 AACR.
authors.affiliation: Service des maladies du sang, Hôpital Huriez, CHRU, Lille France.
authors.forename: Eileen
authors.initials: E
authors.lastname: Boyle
authors.affiliation: Service des maladies du sang, Hôpital Huriez, CHRU, Lille France.
authors.forename: Salomon
authors.initials: S
authors.lastname: Manier
authors.affiliation: DBIM, Hôpital Saint Louis, AP-HP, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Lejeune
authors.affiliation: Service des maladies du sang, Hôpital Huriez, CHRU, Lille France.
authors.forename: Guillemette
authors.initials: G
authors.lastname: Fouquet
authors.affiliation: Service d'Hématologie et Thérapie cellulaire, Hopital La Milétrie, CHU Poitiers, France. Inserm CIC U1402.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Guidez
authors.affiliation: Service des maladies du sang, Hôpital Huriez, CHRU, Lille France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bonnet
authors.affiliation: Service des maladies du sang, Hôpital Huriez, CHRU, Lille France.
authors.forename: Houria
authors.initials: H
authors.lastname: Debarri
authors.affiliation: Service des maladies du sang, Hôpital Huriez, CHRU, Lille France.
authors.forename: Helene
authors.initials: H
authors.lastname: Demarquette
authors.affiliation: Service des maladies du sang, Hôpital Huriez, CHRU, Lille France.
authors.forename: Remy
authors.initials: R
authors.lastname: Dulery
authors.affiliation: Service des maladies du sang, Hôpital Huriez, CHRU, Lille France.
authors.forename: Julie
authors.initials: J
authors.lastname: Gay
authors.affiliation: Service de biochimie spécialisée des protéines, CHRU, Lille France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Hennache
authors.affiliation: Service de biochimie spécialisée des protéines, CHRU, Lille France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Onraed
authors.affiliation: Service de biochimie spécialisée des protéines, CHRU, Lille France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Faucompré
authors.affiliation: Service de biochimie spécialisée des protéines, CHRU, Lille France.
authors.forename: Suzanna
authors.initials: S
authors.lastname: Schraen
authors.affiliation: Service des maladies du sang, Hôpital Huriez, CHRU, Lille France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.affiliation: Hématologie, IUCT Oncopole Toulouse, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.affiliation: DBIM, Hôpital Saint Louis, AP-HP, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.affiliation: Service d'Hématologie, Hôpital La Pitie Salpêtrière, AP-HP, Paris, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Leblond
authors.affiliation: Department of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom. The Binding Site Ltd, Birmingham, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Harding
authors.affiliation: Service d'Hématologie et Thérapie cellulaire, Hopital La Milétrie, CHU Poitiers, France. Inserm CIC U1402. xavier.leleu@chu-poitiers.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
mesh_terms: D000911:Antibodies, Monoclonal / Q000097:blood*; D001809:Blood Viscosity / Q000502:physiology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000097:blood*; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D009391:Nephelometry and Turbidimetry; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M