title: Immunoparesis in IgM gammopathies as a useful biomarker to predict disease progression.
abstract: BACKGROUND
  The management of IgM monoclonal gammopathies undetermined significance (IgM-MGUS) and Waldenstrom's macroglobulinemia (WM) may be challenging. Modern immunoassays that quantify specific monoclonal heavy and light chain immunoglobulins are promising for their use in these applications.
  
  
  METHODS
  Ninety consecutive patients (39 IgM-MGUS, 32 indolent WM [iWM], and 19 WM) seen between January 2007 and March 2014 were analyzed. Heavy/light chain (HLC) and serum free light chains assays (FLC) were determined at diagnosis to study their utility as biomarkers in IgM monoclonal gammopathies.
  
  
  RESULTS
  The HLC involved to uninvolved IgM ratios (iHLC/uHLC) showed a progressive increase when going from IgM-MGUS, to iWM and to WM (p=0.002). Furthermore, an iHLC/uHLC>62 identified a group of iWM patients with a shorter time-to-progression (TTP) (108 vs. 133 months, p=0.033). Separate analysis of the involved and uninvolved components showed that only the suppression of the uninvolvedimmunoglobulin was predictive of shorter TTP (HR=3.04, p=0.03) suggesting that it could be the majorcontributor to the prognostic value of the Hevylite assay. Additionally, a multivariate analysis showed that immunosuppression (either classical immunoparesis or Hevylite immunosuppression) was an independent prognostic factor (p=0.016) reinforcing its relevance in the disease mechanism. Finally, monoclonal sFLC levels were highest in WM patients, with 83% presenting values>60 mg/L.
  
  
  CONCLUSIONS
  The results suggest that the levels of immunosuppression and/or the iHLC/uHLC ratio of IgM immunoglobulins measured by Hevylite are associated with greater disease activity which significantly impacts in the outcome of WM patients and may also help in the differentiation of IgMMGUS from iWM.
authors.affiliation: .
authors.forename: Marcio
authors.initials: M
authors.lastname: Andrade-Campos
authors.affiliation: .
authors.forename: Ilda
authors.initials: I
authors.lastname: Murillo-Flórez
authors.affiliation: .
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.affiliation: .
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000097:blood; D007147:Immunoglobulin Light Chains / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate; D008258:Waldenstrom Macroglobulinemia / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M
keywords: IgM heavy/light chain; IgM monoclonal gammopathy; free light chain