title: Relationship between monoclonal gammopathy and cardiac amyloid type.
abstract: BACKGROUND
  Proper identification of cardiac amyloid type is essential for patient management, and has historically relied upon immunohistochemical- or immunofluorescence-based methods, often correlated with serum and urine protein electrophoresis (SPEP and UPEP) with immunofixation electrophoresis (IFE), and/or free light chain immunoassay (FLC). The recent implementation of mass spectrometry-based proteomic analysis for clinical amyloid typing allows us to determine the validity of these tests to predict amyloid type. Validity of SPEP/UPEP/IFE and FLC assays in cardiac amyloid prediction was examined.
  
  
  METHODS
  Retrospective analysis of two tertiary care populations (n=143, 2001-2010), of cardiac biopsy-proven amyloidosis, was performed.
  
  
  RESULTS
  Amyloid of transthyretin (ATTR) type was found in 81 (57%) of 143 patients and immunoglobulin light chain amyloid was found in the remaining 62 (43%). SPEP/UPEP/IFE detected a monoclonal gammopathy in 76 individuals, 56 with AL and 20 with ATTR amyloid and was overall a poor predictor of AL amyloid in this patient population: specificity (75%; 95% CI, 65-83%) and positive predictive value (PPV 74%; 95% CI, 63-82%). The FLC assay detected an abnormal kappa/lambda ratio in 61 patients, 53 with AL and 8 with ATTR amyloid and was a better predictor of AL amyloid type in this patient population: specificity (90%, 95% CI, 82-95%) and PPV (87%, 95% CI, 76-93%).
  
  
  CONCLUSIONS
  ATTR was the predominant amyloid type in this large cohort of endomyocardial biopsies characterized by mass spectrometry. Although FLC performs better than SPEP/UPEP/IFE, the performance of blood and urine studies for monoclonal proteins are not adequate to classify amyloid type.
  
  
  CONCLUSIONS
  This large-scale retrospective analysis of cardiac amyloidosis shows that blood and urine monoclonal protein studies are not, by themselves, robust predictors of cardiac amyloid type in patients undergoing endomyocardial biopsy.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. maleszewski.joseph@mayo.edu
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Maleszewski
authors.forename: David L
authors.initials: DL
authors.lastname: Murray
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Martha
authors.initials: M
authors.lastname: Grogan
authors.forename: Naveen L
authors.initials: NL
authors.lastname: Pereira
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Jenkins
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.forename: Patrizio
authors.initials: P
authors.lastname: Caturegli
authors.forename: Julie A
authors.initials: JA
authors.lastname: Vrana
authors.forename: Jason D
authors.initials: JD
authors.lastname: Theis
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: Marc K
authors.initials: MK
authors.lastname: Halushka
mesh_terms: D000328:Adult; D000368:Aged; D058227:Amyloidogenic Proteins / Q000032:analysis*; D000686:Amyloidosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D004586:Electrophoresis; D005260:Female; D006331:Heart Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007118:Immunoassay; D007146:Immunoglobulin lambda-Chains / Q000032:analysis; D061346:Laser Capture Microdissection; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D040901:Proteomics / Q000379:methods; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D058227:Amyloidogenic Proteins; D007146:Immunoglobulin lambda-Chains