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Laboratory Support for Diagnosis of Amyloidosis

  • David L. MurrayEmail author
  • Jerry A. Katzmann
Part of the Current Clinical Pathology book series (CCPATH)

Abstract

Serum- and urine-based laboratory testing are important initial observations in helping to guide both the differential diagnosis of primary amyloidosis (AL) and the testing for identifying and characterizing tissue amyloid. The fibrils in AL are derived from intact or fragmented monoclonal immunoglobulin light chains. These patients have intact free monoclonal immunoglobulin and/or free immunoglobulin light chains detected in the serum and/or urine. The purpose of this chapter is to describe the methods used to detect plasma cell proliferation disorders and to identify excess monoclonal free light chain (FLC) synthesis. Specifically, the value of protein electrophoresis (PEL), immunofixation electrophoresis (IFE), and quantitative serum FLC)analysis will be presented. These tests are not only useful in the differential diagnosis of amyloidosis but also have a role in early disease detection, prognosis, and monitoring of AL.

Keywords

Free light chains Serum protein electrophoresis Urine protein electrophoresis Nephelometry Immunofixation electrophoresis Primary (AL) amyloidosis 

References

  1. 1.
    Kyle RA, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Kyle RA, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346(8):564–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Landgren O, et al. Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood. 2006;107(3):904–6.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Rajkumar SV, Gertz MA, Kyle RA. Primary systemic amyloidosis with delayed progression to multiple myeloma. Cancer. 1998;82(8):1501–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Madan S, et al. Clinical features and treatment response of light chain (AL) amyloidosis diagnosed in patients with previous diagnosis of multiple myeloma. Mayo Clin Proc. 2010;85(3):232–8.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Steensma DP. “Congo” red: out of Africa? Arch Pathol Lab Med. 2001;125(2):250–2.PubMedGoogle Scholar
  7. 7.
    Hoffman JE, Hassoun H, Landau H, Comenzo RL. Coincindal gammopathies in patients with systemic amyloidosis and transthyretin gene mutations. Proceedings of the 52nd ASH annual meeting, Orlando, FL; 2010.Google Scholar
  8. 8.
    Strege RJ, Saeger W, Linke RP. Diagnosis and immunohistochemical classification of systemic amyloidosis. Report of 43 cases in an unselected autopsy series. Virchows Arch. 1998;433(1):19–27.CrossRefPubMedGoogle Scholar
  9. 9.
    Gertz MA, Lacy MQ, Dispenzieri A. Amyloidosis: recognition, confirmation, prognosis, and therapy. Mayo Clin Proc. 1999;74(5):490–4.CrossRefPubMedGoogle Scholar
  10. 10.
    Bradwell AR, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem. 2001;47(4):673–80.PubMedGoogle Scholar
  11. 11.
    Katzmann JA, et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002;48(9):1437–44.PubMedGoogle Scholar
  12. 12.
    Barnidge DR, et al. Using mass spectrometry to monitor monoclonal immunoglobulins in patients with a monoclonal gammopathy. J Proteome Res. 2014;13(3):1419–27.CrossRefPubMedGoogle Scholar
  13. 13.
    Drayson M, et al. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood. 2001;97(9):2900–2.CrossRefPubMedGoogle Scholar
  14. 14.
    Lachmann HJ, et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol. 2003;122(1):78–84.CrossRefPubMedGoogle Scholar
  15. 15.
    Abraham RS, et al. Quantitative analysis of serum free light chains. A new marker for the diagnostic evaluation of primary systemic amyloidosis. Am J Clin Pathol. 2003;119(2):274–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Dispenzieri A, et al. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood. 2006;107(8):3378–83.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Katzmann JA, et al. Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice. Clin Chem. 2005;51(5):878–81.CrossRefPubMedGoogle Scholar
  18. 18.
    Bradwell AR, et al. Serum test for assessment of patients with Bence Jones myeloma. Lancet. 2003;361(9356):489–91.CrossRefPubMedGoogle Scholar
  19. 19.
    Katzmann JA, et al. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc. 2006;81(12):1575–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Palladini G, et al. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 2009;55(3):499–504.CrossRefPubMedGoogle Scholar
  21. 21.
    Katzmann JA. Screening panels for monoclonal gammopathies: time to change. Clin Biochem Rev. 2009;30(3):105–11.PubMedCentralPubMedGoogle Scholar
  22. 22.
    Dispenzieri A, et al. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet. 2010;375(9727):1721–8.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Gertz MA, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th international symposium on amyloid and amyloidosis, Tours, France, 18–22 April 2004. Am J Hematol. 2005;79(4):319–28.CrossRefPubMedGoogle Scholar
  24. 24.
    Kumar SK, et al. Changes in serum-free light chain rather than intact monoclonal immunoglobulin levels predicts outcome following therapy in primary amyloidosis. Am J Hematol. 2011;86(3):251–5.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Kumar S, et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood. 2010;116(24):5126–9.PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Yamamoto K, et al. The amyloid fibrils of the constant domain of immunoglobulin light chain. FEBS Lett. 2010;584(15):3348–53.CrossRefPubMedGoogle Scholar
  27. 27.
    Klimtchuk ES, et al. The critical role of the constant region in thermal stability and aggregation of amyloidogenic immunoglobulin light chain. Biochemistry. 2010;49(45):9848–57.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA

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