The assessment of heavy/light chain pairs of immunoglobulin in patients with newly diagnosed Waldenström´s macroglobulinemia
Authors:
T. Pika 1; P. Lochman 2; P. Kušnierová 3; Z. Heřmanová 4; J. Zapletalová 5; P. Puščiznová 1; J. Minařík 1; V. Ščudla 1
Authors‘ workplace:
Hemato-onkologická klinika, LF UP a FN Olomouc
1; Oddělení klinické biochemie, FN Olomouc
2; Oddělení klinické biochemie, Ústav laboratorní diagnostiky, FN Ostrava
3; Ústav imunologie, LF UP a FN Olomouc
4; Ústav lékařské biofyziky a statistiky, LF UP Olomouc
5
Published in:
Klin. Biochem. Metab., 23 (44), 2015, No. 2, p. 42-47
Overview
Introduction:
Waldenström´s macroglobulinemia (WM) is a rare malignant B-lymphoproliferative disorder, characterized by bone marrow infiltration by tumor cells of lymphoplasmocytic lymphoma (LPL) with production of IgM monoclonal immunoglobulin (MIg). The newest test for MIg is the HevyLite system, based on the assessment using the pair of specific antibodies against junction epitopes between the domains of heavy and light chain (HLC) of the constant region of immunoglobulin chains.
Aim:
The aim of our paper was the comparison of detection methods for serum levels of MIg of IgM isotype in patients with newly diagnosed WM using conventional electrophoresis and with the use of the levels of heavy/light chain pairs of the immunoglobulin.
Patients and methods:
Our cohort consisted of 15 sera of WM patients with IgM kappa isotype. The samples were assessed using conventional gel and capillary electrophoresis. The assessment of MIg using gel electrophoresis was carried out using Sebia Hydrasys system, for capillary electrophoresis we used Sebia MiniCap system. For turbidimetry analysis of HLC pairs we used HevyLite Human Ig sets, IgM kappa kit for the use on the SPAplus with the use of turbidimetry SPAplus. For nephelometric analysis of HLC pairs we used nephelometer BN II and HevyLite IgMκ.
Results:
Within the comparison of the levels of MIg using gel (5 – 60 g/l) and capillary (7.5 – 62.5 g/l) electrophoresis we found strong correllation (r = 0.937, p < 0.0001) with median difference 13 %. Median total serum protein concentration was 95.3 g/l (73.4 – 131.6 g/l). Comparison of MIg detected using gel electrophoresis and IgMκ levels detected using SPAplus system (9-155 g/l) and BN II (9.3 – 262 g/l) we found positive correlations (r = 0.928, p < 0.0001), and (r = 0.803; p < 0.001) but with median difference 144 % and 156 % (ICC 0.213). Within the comparison of MIg levels defined by capillary electrophoresis and IgMκ detected by SPAplus system (9 – 155 g/l) and BN II (9.3 – 262 g/l) we found positive correlations (r = 0.959, p < 0.0001) and (r = 0.830; p < 0.001) with median difference 144 % and 133 % (ICC 0.225). The difference rate was increasing with MIg concentration.
Conclusions:
The results of our analysis confirm that the assessment of high IgM concentrations using HLC pairs is accompanied with significant overestimation of the values. Despite relatively strong correlations between conventional electrophoretic methods and HLC assessment, the results exceed not only MIg levels but even total protein levels. The assessment of HLC at this time cannot be reliably used for the diagnostics and monitoring of patients with active WM and high levels of MIg.
Keywords:
Waldenström`s macroglobulinemia, monoclonal immunoglobulin, electrophoresis, heavy/light chain immuno-globulin pairs.
Sources
1. Owen, R. G., Treon, S. P., Al-Katib, A. et al. Clinicopathological definition of Waldenström´s macroglobuli-nemia: Consensus panel recommendations from the second international workshop on Waldenström´s macroglobulinemia. Semin. Oncol., 2003, 30, p. 110 - 115.
2. Vijay, A., Gertz, M. A. Waldenström macroglobuli-nemia. Blood, 2007, 109, p. 5096 – 5103.
3. Gertz, M. A. Waldenström macroglobulinemia: 2013 update on diagnosis, risk stratification, and management. Am. J. Hematol., 2013, 88, p. 704 - 711.
4. Ansell, S. M., Kyle, R. A., Reeder, C. B. et al. Diagnosis and management of Waldenström macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy (mSMART) guidelines. Mayo. Clin. Proc., 2010, 85, p. 824 – 833.
5. Buske, C., Leblond, V. How to manage Waldenstrom’s macroglobulinemia. Leukemia, 2013, 27, p. 762 – 772.
6. Kyle, R. A., Treon, S. P., Alexanian, R. et al. Prognostic markers and criteria to initiate therapy in Waldenström´s macroglobulinemia: consensus panel recommendations from the second international worshop on Waldenström´s macroglobulinemia. Semin. Oncol., 2003, 30, p. 116 - 120.
7. Pika, T., Flodr, P., Novák, M. et al. Klinická problematika IgM monoklonálních gamapatií. Klin. Biochem. Metab., 2014, 22, p. 61 – 64.
8. Kyle, R. A., Dispenzieri, A., Kumar, S., Larson, D., Therneau, T., Rajkumar, S. V. IgM monoclonal gammopathy of undetermined significance (MGUS) and smoldering Waldenström´s macroglobulinemia (SWM). Clin. Lymph. Myeloma ,2011, 11, p. 74 - 76.
9. Salkie, M. L. A retrospective study of the relative utility of electrophoresis, immunoelectrophoresis, immunofixation, and nephelometry in the investigation of serum proteins. Clin. Biochem., 1996, 29, p. 39 - 42.
10. Bailey, D., Lem-Ragosnig, B., Chan, P. C. Challenges in identifying some IgM monoclonal proteins by capillary serum protein electrophoresis. Clin. Biochem., 2013, 46, p. 1776 - 1777.
11. Ščudla, V., Pika, T., Heřmanová, Z. Hevylite – nová analytická metoda v diagnostice a hodnocení průběhu monoklonálních gamapatií. Klin. Biochem. Metab., 2010, 18, p. 62 - 68.
12. Paiva, B., Montes, M. C., Garcia-Sanz, R. et al. Multiparameter flow cytometry for the identification of the Waldenström´s clone in IgM-MGUS and Waldenström´s macroglobulinemia: new criteria for differential diagnosis and risk stratification. Leukemia, 2014, 28, p. 166 - 173.
13. De Tute, R. M., Rawstron, A. C., Owen, R. G. Immunoglobulin M concentration in Waldenström macroglobulinemia: correlation with bone marrow B cells and plasma cells. Clin. Lymph. Myeloma, 2013, 13, p. 211 – 213.
14. Tripsas, C. K., Patterson, C. J., Uljon, S. N., Lindenman, N. I., Turnbull, B., Treon, S. P. Comparative response assessment by serum immunoglobulin M M-protein and total serum immunoglobulin M after treatment of patients with Waldenström macroglobulinemia. Clin. Lymph. Myeloma, 2013, 13, p. 250 – 252.
15. Uljon, S. N., Treon, S. P., Tripsas, C. K., Lindenman, N. L. Challenges with serum protein electrophoresis in assessing progression and clinical response in patients with Waldenström macroglobulinemia. Clin. Lymph. Mye-loma, 2013, 13, p. 247 – 249.
16. Koulieris, E., Kyrtsonis, M-C, Maltezas, M. et al. Quantification of serum IgMκ and IgMλ in patients with Waldenström`s macroglobulinemia (WM) at diagnosis and during disease course; clinical correlations. Blood, 2010, 116, Abstract 3004.
17. Leleu, X. Koulieris, E., Maltezas, D. et al. Novel M-component based biomarkers in Waldenström`s macroglobulinemia. Clin. Lymph. Myeloma, 2011, 11, p. 164 – 167.
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