Monitoring IgA Multiple Myeloma: Immunoglobulin Heavy/Light Chain Assays

Katzmann, Jerry A.; Willrich, Maria Alice V.; Kohlhagen, Mindy; Kyle, Robert A.; Murray, David; Snyder, Melissa R.; Rajkumar, S. Vincent; Dispenzieri, Angela

doi:10.1373/clinchem.2014.231985

Cited by 57 publications

(62 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Katzmann et al's study recommended use of the IgA heavy/light measurement for β-migrating IgA M-proteins, however, they did not see an advantage to using the IgG heavy/light measurements in preference to the M-spike measurement for these β region bands [52]. One would suspect that β-migrating IgG or IgM M-spikes would also benefit from the more precise heavy/light chain measurement.…”

Section: Nephelometry and Turbidimetry For Heavy-light Chain Combinatmentioning

confidence: 99%

“…However, other isotypes occasionally migrate in the β or α regions and also present difficulties in measurement by the tangent method. Because of the variabilities involved in measuring the β migrating IgA M-spikes when using relatively low resolution gel techniques, Katzmann et al do not measure symmetric IgA β M-spikes smaller than 20 g/L (2.0 g/dL) [52]. Recognizing these issues, the 2014 IMWG guidelines recommend measurement of total IgA rather than the M-protein spike to follow patients with β-migrating IgA M-proteins [53].…”

Section: Detection and Measurement Of M-proteins In Serum By Protein mentioning

confidence: 99%

“…An alternative to measuring the β-migrating IgA M-spike could be, nephelometric measurement of the heavy-light chain pairs for IgA (IgAK separately from IgAL), which Katzmann et al have shown to provide superior results to those from the standard perpendicular drop measurements of gel electrophoretic traces in the β region [52].…”

Section: A B Cmentioning

confidence: 99%

“…This permits one to estimate the amount of M-protein and can inform the corrected perpendicular drops as shown in Figure 4B. While such methods are subjective and are correctly termed estimates, the immunochemical measurements of total immunoglobulin of the involved isotype as suggested by Ludwig et al, or even heavy-light chain pairs as performed by Katzmann et al [52], also include incalculable amounts of polyclonal immunoglobulins of that isotype or heavy-light chain pair. As with the perpendicular drop, quantification of M-protein using these methods is more substantially distorted the more the M-protein declines and normal clones recover after therapy.…”

Section: A B Cmentioning

confidence: 99%

“…This finding suggests that the 95% range was too narrow as a diagnostic reference range. Once again, Katzmann et al developed a confidence interval (99%) that improved the specificity of this assay [52]. If one were to apply the 99% confidence interval of 0.53-2.52 to the study of Ludwig et al, only one of the two cases would have been positive, but that sample had a total IgAK (the involved heavy/light chain pair) measuring only 1.25 g/L (125 mg/dL), well within the normal range of 0.43-2.36 g/L (43-236 mg/dL) [87].…”

Section: Nephelometry and Turbidimetry For Heavy-light Chain Combinatmentioning

confidence: 99%

See 4 more Smart Citations

Challenges of measuring monoclonal proteins in serum

Keren

Schroeder

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

Abstract:The measurement of monoclonal protein (M-protein) is vital for stratifying risk and following individuals with a variety of monoclonal gammopathies. Direct measurement of the M-protein spike by electrophoresis and immunochemical measurements of specific isotypes or free light chains pairs has provided useful information about the quantity of M-protein. Nonetheless, both traditional electrophoresis and immunochemical methods give poor quantification with M-proteins smaller than 10 g/L (1 g/dL) when in the presence of polyclonal immunoglobulins that co-migrate with the M-protein. In addition, measurements by electrophoresis of M-proteins migrating in the β-and α-regions are contaminated by normal serum proteins in those regions. The most precise electrophoretic method to date for quantification involves exclusion of the polyclonal immunoglobulins by using the tangent skimming method on electropherograms, which provides a 10-fold improvement in precision. So far, however, tangent measurements are limited to γ migrating M-proteins. Another way to improve M-protein measurements is the use of capillary electrophoresis (CE). With CE, one can employ immunosubtraction to select a region of interest in the β region thereby excluding much of the normal proteins from the M-protein measurement. Recent development of an immunochemical method distinguishing heavy/light chain pairs (separately measuring IgGK and IgGL, IgAK and IgAL, and IgMK and IgML) provides measurements that could exclude polyclonal contaminants of the same heavy chain with the uninvolved light chain type. Yet, even heavy/light results contain an immeasurable quantity of polyclonal heavy/ light chains of the involved isotype. Finally, use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) looms on the horizon as a means to provide more consistent and sensitive measurements of M-proteins.

show abstract

Section: Nephelometry and Turbidimetry For Heavy-light Chain Combinatmentioning

confidence: 99%

Section: Detection and Measurement Of M-proteins In Serum By Protein mentioning

confidence: 99%

Section: A B Cmentioning

confidence: 99%

Section: A B Cmentioning

confidence: 99%

Section: Nephelometry and Turbidimetry For Heavy-light Chain Combinatmentioning

confidence: 99%

See 3 more Smart Citations

Challenges of measuring monoclonal proteins in serum

Keren

Schroeder

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

show abstract

Biomarkers of minimal residual disease in rituximab‐treated patients with mixed cryoglobulinemia

Basile

Gulli

Napodano

et al. 2020

Biotech and App Biochem

View full text Add to dashboard Cite

Hepatitis C virus (HCV) represents the major risk factor for mixed cryoglobulinemia (MC), a small‐vessel vasculitis that may evolve into an overt B‐cell non‐Hodgkin's lymphoma. Here, we aimed to identify a biomarker signature for the early diagnosis of minimal residual disease (MRD). We assessed free light chains (FLCs), IgM k,and IgM λ heavy/light chain (HLC) pairs, and vascular endothelial growth factor (VEGF) in sera from 34 patients with MC vasculitis (32 HCV‐ and 2 HBV‐related), treated with low‐dose rituximab (RTX). FLCs and IgM HLCs were measured by turbidimetric assay; VEGF by an enzyme‐linked immunosorbent assay. After RTX, the positive (complete + partial) clinical and laboratory responses were of 85.29% and 50%, respectively; in contrast, the mean levels of FLCs, IgM HLCs, and VEGF were substantially unaffected in most patients and still above the normal range. In those achieving a reduction of FLCs and IgM k and λ chains values within the range of normality, we found that post‐treatment free λ chains and IgM k values correlated with clinical and laboratory response. Our results suggest that high levels of FLCs, IgM HLCs, and VEGF could represent the signature of “dormant” B cell clones’ activity that could be very useful to identify MRD indicative of possible relapse or worsening outcome.

show abstract

Detection of the value of consecutive serum total light chain (sTLC) in patients diagnosed with diffuse large B cell lymphoma

et al. 2016

View full text Add to dashboard Cite

There are limited data on serum total light chain (sTLC) in lymphoma and its relative role on the outcome of diffuse large B cell lymphoma (DLBCL) patients. Blood samples from 46 cases newly diagnosed with DLBCL were collected consecutively during chemotherapy to detect sTLC, IgG, IgA, and IgM levels. Clinical data and survival outcomes were analyzed according to the results of sTLC measurements. In summary, 22 patients (47.8 %) had abnormal k or λ light chain, respectively, and 6 patients (13.0 %) had both abnormal k and λ light chains before chemotherapy. Patients with elevated k light chain more frequently displayed multiple extra-nodal organ involvement (P = 0.01) and had an inferior overall survival (OS) (P = 0.041) and progression-free survival (PFS) (P = 0.044) compared to patients with normal level of k light chain. Furthermore, patients with elevated level of both k and λ also exhibited significant association with shorter OS (P = 0.002) and PFS (P = 0.009). Both elevated k alone and concurrent elevated k and λ had independent adverse effects on PFS (P = 0.031 and P = 0.019, respectively). sTLC level was reduced gradually by treatment in this study and reached the lowest point after the fourth cycle of chemotherapy, which was consistent with the disease behavior during chemotherapy. Considering the small sample size of this study, these results should be confirmed in a larger prospective study.

show abstract

Monitoring IgA Multiple Myeloma: Immunoglobulin Heavy/Light Chain Assays

Cited by 57 publications

References 16 publications

Challenges of measuring monoclonal proteins in serum

Challenges of measuring monoclonal proteins in serum

Biomarkers of minimal residual disease in rituximab‐treated patients with mixed cryoglobulinemia

Detection of the value of consecutive serum total light chain (sTLC) in patients diagnosed with diffuse large B cell lymphoma

Contact Info

Product

Resources

About