Optimization of Serum Immunoglobulin Free Light Chain Analysis for Subclassification of Cardiac Amyloidosis.
Accurate and rapid classification of cardiac amyloidosis is important for patient management. We have optimized the use of serum free light chain kappa and lambda values to differentiate immunoglobulin light chain amyloid (AL) amyloidosis from transthyretin amyloid and amyloid A using 85 cases of tissue-proven cardiac amyloidosis, in which there was direct classification of amyloidosis by mass spectrometry or immunofluorescence. The serum free light chain kappa/lambda ratios were non-overlapping for the three major groups: AL-lambda (0.01-0.41, n = 30), non-AL (0.52-2.7, n = 43), and AL-kappa (6.7-967, n = 12). A kappa/lambda ratio value between 0.5 and 5.0 had 100 % sensitivity and 100 % specificity for distinguishing AL amyloidosis from non-AL amyloidosis. This optimized range for serum light chain kappa/lambda ratio provides extremely robust classification of cardiac amyloidosis. Cases of cardiac amyloidosis in which the serum kappa/lambda free light chain ratio falls close to these new cutoff values may benefit most from direct amyloid subtyping.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Marc K
MK
Halushka
George
G
Eng
A Bernard
AB
Collins
Daniel P
DP
Judge
Marc J
MJ
Semigran
James R
JR
Stone
D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D000686:Amyloidosis / Q000097:blood* / Q000145:classification / Q000175:diagnosis / Q000276:immunology; D015142:Baltimore; D015415:Biomarkers / Q000097:blood; D001900:Boston; D009202:Cardiomyopathies / Q000097:blood* / Q000145:classification / Q000175:diagnosis / Q000276:immunology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000097:blood*; D007146:Immunoglobulin lambda-Chains; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology; D011237:Predictive Value of Tests; D000685:Serum Amyloid A Protein / Q000032:analysis
D015415:Biomarkers; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D000685:Serum Amyloid A Protein