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Chapter 11 : Strategy for Detecting and Following Monoclonal Gammopathies

Authors: Jerry A. Katzmann1, David F. Keren2
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Affiliations: 1: Mayo Clinic and Mayo Foundation, Laboratory Medicine and Pathology, 200 First St. SW, Rochester, MN 55905; 2: University of Michigan, 5228 Medical Science I, 1301 Catherine, Ann Arbor, MI 48109
Content Type: Reference
Publication Year: 2016

Category: Immunology

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Abstract:

The preceding chapters in this section have dealt with several aspects of serum and urine protein analysis for immunoglobulins. Overwhelmingly, the single most important reason for performing these studies is to detect monoclonal gammopathies. This chapter briefly summarizes the various plasma cell proliferative diseases and then describes the use of the electrophoretic and nephelometric assays for the diagnosis, prognosis, and monitoring of monoclonal gammopathies. There are some general strategies for all laboratories as well as specific tests that are needed, depending on the disease presentation.

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
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Strategy for Detecting and Following Monoclonal Gammopathies
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Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
/content/10.1128/9781555818722.ch11.ch11fig1
FIGURE 1

Normal serum protein electrophoresis (PEL) and immunofixation electrophoresis (IFE). The gel scan (electropherogram) is aligned above the PEL gel. Alb, albumin; ELP, electropherogram.

10.1128/9781555818722/8722ch11fig1_thmb.gif
10.1128/9781555818722/8722ch11fig1.gif
Image of FIGURE 1
FIGURE 1

Normal serum protein electrophoresis (PEL) and immunofixation electrophoresis (IFE). The gel scan (electropherogram) is aligned above the PEL gel. Alb, albumin; ELP, electropherogram.

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
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FIGURE 2

Monoclonal gammopathy serum protein electrophoresis (PEL) and immunofixation electrophoresis (IFE). The gel scan (electropherogram) is aligned above the PEL gel. The dashed lines on both sides of the M protein indicate the M-spike fraction.

10.1128/9781555818722/8722ch11fig2_thmb.gif
10.1128/9781555818722/8722ch11fig2.gif
Image of FIGURE 2
FIGURE 2

Monoclonal gammopathy serum protein electrophoresis (PEL) and immunofixation electrophoresis (IFE). The gel scan (electropherogram) is aligned above the PEL gel. The dashed lines on both sides of the M protein indicate the M-spike fraction.

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
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FIGURE 3

Light-chain multiple myeloma serum (left) and urine (right) tested by PEL and IFE.

10.1128/9781555818722/8722ch11fig3_thmb.gif
10.1128/9781555818722/8722ch11fig3.gif
Image of FIGURE 3
FIGURE 3

Light-chain multiple myeloma serum (left) and urine (right) tested by PEL and IFE.

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
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FIGURE 4

Primary amyloid tested by serum (left) and urine (right) PEL and IFE.

10.1128/9781555818722/8722ch11fig4_thmb.gif
10.1128/9781555818722/8722ch11fig4.gif
Image of FIGURE 4
FIGURE 4

Primary amyloid tested by serum (left) and urine (right) PEL and IFE.

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
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FIGURE 5

Large M protein with suppressed polyclonal immunoglobulins.

10.1128/9781555818722/8722ch11fig5_thmb.gif
10.1128/9781555818722/8722ch11fig5.gif
Image of FIGURE 5
FIGURE 5

Large M protein with suppressed polyclonal immunoglobulins.

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
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/content/10.1128/9781555818722.ch11.ch11fig6
FIGURE 6

Small M protein within a background of polyclonal immunoglobulins.

10.1128/9781555818722/8722ch11fig6_thmb.gif
10.1128/9781555818722/8722ch11fig6.gif
Image of FIGURE 6
FIGURE 6

Small M protein within a background of polyclonal immunoglobulins.

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
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FIGURE 7

(A) Use of ISE to estimate the area of small beta-migrating M proteins. Capillary electropherogram with beta region restriction and hypogammaglobulinemia. (B) Immunosubtraction demonstrating that anti-IgA and anti-L subtract the M protein in the mid-beta region. (C) Use ISE data to demarcate and measure the M protein concentration.

10.1128/9781555818722/8722ch11fig7_thmb.gif
10.1128/9781555818722/8722ch11fig7.gif
Image of FIGURE 7
FIGURE 7

(A) Use of ISE to estimate the area of small beta-migrating M proteins. Capillary electropherogram with beta region restriction and hypogammaglobulinemia. (B) Immunosubtraction demonstrating that anti-IgA and anti-L subtract the M protein in the mid-beta region. (C) Use ISE data to demarcate and measure the M protein concentration.

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
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Tables

Strategy for Detecting and Following Monoclonal Gammopathies
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Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
/content/10.1128/9781555818722.ch11.ch11tab1
TABLE 1

Monoclonal gammopathies from the Mayo Clinic, 1960 to 2008

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TABLE 1

Monoclonal gammopathies from the Mayo Clinic, 1960 to 2008

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
/content/10.1128/9781555818722.ch11.ch11tab2
TABLE 2

Distribution of monoclonal proteins in patients with multiple myeloma and monoclonal gammopathies of undetermined significance

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TABLE 2

Distribution of monoclonal proteins in patients with multiple myeloma and monoclonal gammopathies of undetermined significance

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
/content/10.1128/9781555818722.ch11.ch11tab3
TABLE 3

Diagnostic sensitivities of monoclonal gammopathy screening panels with combinations of serum PEL, serum IFE, serum FLC, and/or urine IFE-PEL

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TABLE 3

Diagnostic sensitivities of monoclonal gammopathy screening panels with combinations of serum PEL, serum IFE, serum FLC, and/or urine IFE-PEL

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
/content/10.1128/9781555818722.ch11.ch11tab4
TABLE 4

Response criteria for FLC determination

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TABLE 4

Response criteria for FLC determination

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11
/content/10.1128/9781555818722.ch11.ch11tab5
TABLE 5

International Myeloma Working Group criteria for response to therapy

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TABLE 5

International Myeloma Working Group criteria for response to therapy

Citation: Katzmann J, Keren D. 2016. Strategy for Detecting and Following Monoclonal Gammopathies, p 112-124. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch11

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