title: Increased serum free light chains precede the presentation of immunoglobulin light chain amyloidosis.
abstract: OBJECTIVE
  Patients with immunoglobulin light chain amyloidosis (AL amyloidosis) generally present with advanced organ dysfunction and have a high risk of early death. We sought to characterize monoclonal immunoglobulin (M-Ig) light chains before clinical presentation of AL amyloidosis.
  
  
  METHODS
  We obtained prediagnostic sera from 20 cases with AL amyloidosis and 20 healthy controls matched for age, sex, race, and age of serum sample from the Department of Defense Serum Repository. Serum protein electrophoresis with immunofixation and serum free light chain (FLC) analysis were performed on all samples.
  
  
  RESULTS
  An M-Ig was detected in 100% of cases and 0% of controls (P < .001). The M-Ig was present in 100%, 80%, and 42% of cases at less than 4 years, 4 to 11 years, and more than 11 years before diagnosis, respectively. The median FLC differential (FLC-diff) was higher in cases compared with controls at all time periods, less than 4 years (174.8 v 0.3 mg/L; P < .001), 4 to 11 years (65.1 v 2.2 mg/L; P < .001), and more than 11 years (4.5 v 0.4 mg/L; P = .03) before diagnosis. The FLC-diff was greater than 23 mg/L in 85% of cases and 0% of controls (P < .001). The FLC-diff level increased more than 10% per year in 84% of cases compared with 16% of controls (P < .001).
  
  
  CONCLUSIONS
  Increase of FLCs, including within the accepted normal range, precedes the development of AL amyloidosis for many years.
authors.affiliation: Brendan M. Weiss, University of Pennsylvania, Philadelphia, PA; Joseph Hebreo, Naval Medical Center San Diego, San Diego, CA; Daniel V. Cordaro, Mark J. Roschewski, Thomas Baker, Kevin C. Abbott, and Stephen W. Olson, Walter Reed National Military Medical Center, Bethesda, MD. brendan.weiss@uphs.upenn.edu.
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Weiss
authors.affiliation: Brendan M. Weiss, University of Pennsylvania, Philadelphia, PA; Joseph Hebreo, Naval Medical Center San Diego, San Diego, CA; Daniel V. Cordaro, Mark J. Roschewski, Thomas Baker, Kevin C. Abbott, and Stephen W. Olson, Walter Reed National Military Medical Center, Bethesda, MD.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hebreo
authors.affiliation: Brendan M. Weiss, University of Pennsylvania, Philadelphia, PA; Joseph Hebreo, Naval Medical Center San Diego, San Diego, CA; Daniel V. Cordaro, Mark J. Roschewski, Thomas Baker, Kevin C. Abbott, and Stephen W. Olson, Walter Reed National Military Medical Center, Bethesda, MD.
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Cordaro
authors.affiliation: Brendan M. Weiss, University of Pennsylvania, Philadelphia, PA; Joseph Hebreo, Naval Medical Center San Diego, San Diego, CA; Daniel V. Cordaro, Mark J. Roschewski, Thomas Baker, Kevin C. Abbott, and Stephen W. Olson, Walter Reed National Military Medical Center, Bethesda, MD.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Roschewski
authors.affiliation: Brendan M. Weiss, University of Pennsylvania, Philadelphia, PA; Joseph Hebreo, Naval Medical Center San Diego, San Diego, CA; Daniel V. Cordaro, Mark J. Roschewski, Thomas Baker, Kevin C. Abbott, and Stephen W. Olson, Walter Reed National Military Medical Center, Bethesda, MD.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Baker
authors.affiliation: Brendan M. Weiss, University of Pennsylvania, Philadelphia, PA; Joseph Hebreo, Naval Medical Center San Diego, San Diego, CA; Daniel V. Cordaro, Mark J. Roschewski, Thomas Baker, Kevin C. Abbott, and Stephen W. Olson, Walter Reed National Military Medical Center, Bethesda, MD.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Abbott
authors.affiliation: Brendan M. Weiss, University of Pennsylvania, Philadelphia, PA; Joseph Hebreo, Naval Medical Center San Diego, San Diego, CA; Daniel V. Cordaro, Mark J. Roschewski, Thomas Baker, Kevin C. Abbott, and Stephen W. Olson, Walter Reed National Military Medical Center, Bethesda, MD.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Olson
mesh_terms: D000328:Adult; D000686:Amyloidosis / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D007147:Immunoglobulin Light Chains