Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies

Tate, Jillian R.; Graziani, Maria Stella; Mollee, Peter; Merlini, Giampaolo

doi:10.1515/cclm-2016-0268

Cited by 3 publications

(1 citation statement)

References 42 publications

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“…This is most likely attributed to the specific migration of this M-protein which had its peak separate from the rest of the beta fraction. One way to improve the accuracy of low-concentration M-proteins is to quantify isotype-specific immunoglobulin classes [21]. This can be especially useful with betamigrating IgAs overlapping with other proteins.…”

Section: Discussionmentioning

confidence: 99%

An international multi-center serum protein electrophoresis accuracy and M-protein isotyping study. Part I: factors impacting limit of quantitation of serum protein electrophoresis

Turner

Frinack

Ettore

et al. 2020

Clinical Chemistry and Laboratory Medicine (CCLM)

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BackgroundSerum protein electrophoresis (SPEP) is used to quantify the serum monoclonal component or M-protein, for diagnosis and monitoring of monoclonal gammopathies. Significant imprecision and inaccuracy pose challenges in reporting small M-proteins. Using therapeutic monoclonal antibody-spiked sera and a pooled beta-migrating M-protein, we aimed to assess SPEP limitations and variability across 16 laboratories in three continents.MethodsSera with normal, hypo- or hypergammaglobulinemia were spiked with daratumumab, Dara (cathodal migrating), or elotuzumab, Elo (central-gamma migrating), with concentrations from 0.125 to 10 g/L (n = 62) along with a beta-migrating sample (n = 9). Provided with total protein (reverse biuret, Siemens), laboratories blindly analyzed samples according to their SPEP and immunofixation (IFE) or immunosubtraction (ISUB) standard operating procedures. Sixteen laboratories reported the perpendicular drop (PD) method of gating the M-protein, while 10 used tangent skimming (TS). A mean percent recovery range of 80%–120% was set as acceptable. The inter-laboratory %CV was calculated.ResultsGamma globulin background, migration pattern and concentration all affect the precision and accuracy of quantifying M-proteins by SPEP. As the background increases, imprecision increases and accuracy decreases leading to overestimation of M-protein quantitation especially evident in hypergamma samples, and more prominent with PD. Cathodal migrating M-proteins were associated with less imprecision and higher accuracy compared to central-gamma migrating M-proteins, which is attributed to the increased gamma background contribution in M-proteins migrating in the middle of the gamma fraction. There is greater imprecision and loss of accuracy at lower M-protein concentrations.ConclusionsThis study suggests that quantifying exceedingly low concentrations of M-proteins, although possible, may not yield adequate accuracy and precision between laboratories.

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Section: Discussionmentioning

confidence: 99%

An international multi-center serum protein electrophoresis accuracy and M-protein isotyping study. Part I: factors impacting limit of quantitation of serum protein electrophoresis

Turner

Frinack

Ettore

et al. 2020

Clinical Chemistry and Laboratory Medicine (CCLM)

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IgE-kappa multiple myeloma with kappa free light chain: a case report

Hu,

Shao,

Pan

et al. 2024

Scandinavian Journal of Clinical and Laboratory Investigation

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Risk stratification of smoldering multiple myeloma: predictive value of free light chains and group-based trajectory modeling

Moshier

Leng

et al. 2018

Blood Advances

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We investigated the predictive role for serum free light chain ratio (FLCr) ≥100, bone marrow plasma cell (BMPC) ≥60%, and evolving biomarkers through group-based trajectory modeling (GBTM) as high-risk defining events in 273 smoldering multiple myeloma (SMM) patients with a median follow-up of 74 months. FLCr ≥100 was confirmed as a marker for high-risk progression with a median time to progression (TTP) of 40 months with a 44% risk of progression of disease (PD) at 2 years; however, 44% of FLCr ≥100 also did not progress during follow-up. For patients with BMPC ≥60% by core biopsy, the median TTP was 31 months with a 2-year PD of 41%. GBTM established high-risk trajectories for evolving hemoglobin (eHb; characterized as a 1.57 g/dL decrease in hemoglobin), evolving m-protein (eMP; 64% increase in m-protein), and evolving differences in FLC (edFLC; 169% increase in dFLC) within 1 year of diagnosis associated with a decreased median TTP and an increased 2 year rate of PD. Of all the variables examined, we identify a model where immunoparesis, eHb, eMP, and edFLC were significant predictors for ultra-high-risk progression with a median TTP of only 13 months with 3 or more variables present. Our results not only confirm a more modest 2 year PD associated with FLCr ≥100 and BMPC ≥60 but also suggest that eHb, eMP, and edFLC may help identify an ultra-high-risk SMM group.

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Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies

Cited by 3 publications

References 42 publications

An international multi-center serum protein electrophoresis accuracy and M-protein isotyping study. Part I: factors impacting limit of quantitation of serum protein electrophoresis

An international multi-center serum protein electrophoresis accuracy and M-protein isotyping study. Part I: factors impacting limit of quantitation of serum protein electrophoresis

IgE-kappa multiple myeloma with kappa free light chain: a case report

Risk stratification of smoldering multiple myeloma: predictive value of free light chains and group-based trajectory modeling

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