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Optimization of Serum Immunoglobulin Free Light Chain Analysis for Subclassification of Cardiac Amyloidosis

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Abstract

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.

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Abbreviations

AA:

Amyloid A

AL:

Immunoglobulin light chain amyloid

ATTR:

Transthyretin amyloid

SFLC:

Serum free light chain

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Acknowledgments

This study was funded by Massachusetts General Hospital and The Johns Hopkins Hospital.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study formal, consent is not required.

This article does not contain any studies with animals performed by any of the authors.

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Authors and Affiliations

  1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Marc K. Halushka

  2. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    George Eng & A. Bernard Collins

  3. Department of Medicine, Cardiology Division, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Daniel P. Judge

  4. Department of Medicine, Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Marc J. Semigran

  5. Center for Systems Biology, Massachusetts General Hospital and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Room 8236, 185 Cambridge Street CPZN, Boston, MA, 02114, USA

    James R. Stone

Authors
  1. Marc K. Halushka
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  2. George Eng
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  3. A. Bernard Collins
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  4. Daniel P. Judge
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  6. James R. Stone
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Correspondence to James R. Stone.

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Editor-in-Chief Jennifer L. Hall oversaw the review of this article.

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Halushka, M.K., Eng, G., Collins, A.B. et al. Optimization of Serum Immunoglobulin Free Light Chain Analysis for Subclassification of Cardiac Amyloidosis. J. of Cardiovasc. Trans. Res. 8, 264–268 (2015). https://doi.org/10.1007/s12265-015-9628-2

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  • DOI: https://doi.org/10.1007/s12265-015-9628-2

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