Comparison of the serum levels of heavy/light chain pairs of immunoglobulin (Hevylite™) and analysis of parameters of bone metabolism in patients with multiple myeloma.
Authors:
P. Krhovská 1; Z. Heřmanová 2; P. Petrová 3; J. Zapletalová 4; T. Pika 1; J. Bačovský 1; V. Ščudla 1; J. Minařík 1
Authors‘ workplace:
Hemato-onkologická klinika LF UP a FN Olomouc
1; Ústav imunologie, LF UP a FN Olomouc
2; Oddělení klinické biochemie FN a LF UP Olomouc
3; Ústav lékařské biofyziky, LF UP Olomouc
4
Published in:
Klin. Biochem. Metab., 25, 2017, No. 1, p. 13-17
Overview
Objective:
Our aim was to assess serum levels of heavy/light chain pairs of immunoglobulin (HLC) and to compare them with the parameters of myeloma bone disease (MBD) signaling in patients with multiple myeloma (MM).
Materials and methods:
Our 55 patients cohort consisted of patients with newly diagnosed multiple myeloma, 37 with the presence of M-protein IgG and 18 with the presence of M-protein IgA. At the time of diagnosis we measured serum levels of heavy/light chain pairs of immunoglobulin (using Hevylite™ technique) and involved/uninvolved heavy chain ratio (HLC-r) in comparison with serum levels of parameters of MBD signaling and bone marrow microenvironment: Hepatocyte growth factor (HGF), Macrophage inflammatory factor 1 (MIP-1), syndecan-1/CD138 (SYN), Dickkopf-1-related protein (DKK-1), osteoprotegerin (OPG), Activin A, Annexin A2, Nuclear factor kappa B (NF-κB). We also investigated the relationship between the level of HLC and the extent of MM evaluated by Durie-Salmon staging system (D-S).
Results:
Serum levels of heavy/light chain pairs of immunoglobulin were found to correlate with some parameters of bone microenvironment: We found significant relationship of HLC IgG-κ and HLC-r to HGF (correlation coefficient - cc=0.424, p=0.044) and also the relationship between HLC IgA-κ and HLC-r to OPG (cc=0.697, p=0.025). All the other parameters of MBD were independent of HLC levels, and there was no relationship of HLC levels to the extent of MM assessed by D-S.
Conclusion:
Hevylite™ method is a perspective auxiliary diagnostic test in multiple myeloma. Our results document the relationship of serum levels of HLC and selected indicators of MBD independent of the extent on the disease. The assessment of HLC therefore seems to be a promising tool also for the assessment of the relationship to myeloma bone disease.
Keywords:
multiple myeloma, levels of heavy/light chains of immunoglobulin, pairs of heavy/light chains of immunoglobulin, Hevylite, myeloma bone disease, bone marrow microenvironment.
Sources
1. Rajkumar, S. V., Dimopoulos, M. A., Palumbo, A. et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Onc., 2014, 15, p. 538-548.
2. Roodman, G. D. Pathogenesis of myeloma bone disease. Leukemia, 2009, 23, p. 35-441.
3. Mundy, G. R., Raisz, L. G., Cooper, R. A. et al. Evidence for the secretion of an osteoclast stimulating factor in myeloma. N Engl. J Med., 1974, 291, p. 1041-1046.
4. Bradwell, A. R., Harding, S. J., Fourrier, N. J. et al. Assessment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios. Clin. Chem., 2009, 55, p. 1646-1655.
5. Ščudla, V., Pika, T., Heřmanová, Z. et al. Hevylite – nová analytická metoda v diagnostice a hodnocení průběhu monoklonálích gamapatii. Klin. Biochem. Metabol., 2010, 18, p. 62-68.
6. Bradwell, A. R. Analysis of immunoglobulin heavy chain/light chain pairs (HevyliteTM ). In: Bradwell AR. Serum free light chain analysis (plus Hevylite). 6th edition, UK, The Binding Site Ltd. 2010, p. 301–320. ISBN: 978-0-9932196-0-3
7. Ludwig, H., Milosavljevic, D., Zojer, N. et al. Immunoglobulin heavy/light chain ratios improve paraprotein detection and monitoring, identify residual disease and correlate with survival in multiple myeloma patients. Leukemia, 2013, p. 213-219.
8. Minařík, J., Pika, T., Bačovský, J. et al. Prognostic value of hepatocyte growth factor, syndecan-1, and osteopontin in multiple myeloma and monoclonal gammopathy of undetermined significance. Scien. W. J., 2012, p. 356128.
9. Durie, B. G., Salmon, S. E. A clinical staging system for multiple myeloma, Correlation of Measured Myeloma Cell Mass with Presenting. Cancer, 1975, 36, p. 842-854.
10. Ščudla, V., Budíková, M., Pika, T. et al. Srovnání sérových hladin vybraných biologických působků u monoklonální gamapatie nejistého významu a mnohočetného myelomu. Čas. Lek. Čes., 2009, 148, p. 315–322.
11. Hájek, R., Adam, Z., Ščudla, V. et al. Souhrn doporučení CMG 2012 „Diagnostika a léčba mnohočetného myelomu“. Transfuze Hematol. Dnes., 2012, 18, p. 5-89.
12. Vávrová, J. Stanovení volných lehkých řetězců a Hevylite™ u monoklonálních gamapatií. In: Maisnar V, Tichy M, et al. Monoklonální imunoglobuliny – výskyt, význam a možnosti jejich průkazu. Hradec Králové: Nucleus, 2012, p. 55-60, ISBN: 978-80-87009-87-1.
13. Keren, D. F. Heavy/Light-chain analysis of monoclonal gammopathies. Clin. Chem., 2009, 55, p. 1606-1608.
14. Bradwell, A. R., Harding, S., Fourrier, N. J. et al. Assesment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios. Clin. Chem., 2009, 55, p. 1646–1655.
15. Wolff, F., Debaugnies, F., Rozen, L. et al. Assessment of the diagnostic performance of IgA heavy and light chain pairs in patiens with IgA monoclonal gammopathy. Clin. Biochem., 2013, 46, p. 79–84.
16. Koulieris, E., Panayiotidis, P., Harding, S. J. et al. Ratio of involved/unilvolved immunoglobulin quantification by Hevylite™ assay: clinical and prognostic impact in multiple myeloma. Experimental Hematol and Oncology, 2012, 1, p. 9-16.
17. Lakomy, D., Lemaire – Ewing, S., Denimal, D. et al. Evaluation of the new Hevylite™ IgA assay for the diagnosis and follow – up of monoclonal gammopathies. Ann. Biol. Clin., 2013, 71, p. 157–163.
18. Saad, F., Lipton, A., Cook, R. et al. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer, 2007, 110, p. 1860-1867.
19. Bussolino, F., Di Renzo, M. F., Ziche, M. et al. Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J Cell. Biol., 1992, 119, p. 629-641.
20. Sato, T., Hakeda, Y., Yamaguchi, Y. et al. Hepatocyte growth factor is involved in formation of osteoclast-like cells mediated by clonal stromal cells (MC3T3-G2/PA6). J Cell Physiol., 1995, 164, p. 197-204.
21. Lacey, D. L., Timms, E., Tan, H. L. et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell., 1998, 93, p. 165-176.
22. Ščudla, V., Budíková, M., Pika, T. et al. Srovnání sérových hladin vybraných biologických ukazatelů u monoklonální gamapatie nejistého významu a mnohočetného myelomu. Vnitř. Lek., 2006, 52, p. 232-240.
23. Katzmann, J., Clark, R., Kyle, R. A. et al. Supression of uninvolved immunoglobulins defined by heavy/light chain pair supression is a risk factor for progression of MGUS. Leukemia, 2013, 27, p. 208–212.
24. Minařík, J., Golová, Z., Petrová, P. et al. Serum levels of the selected parameters od bone microenvironment predict overall survival in multiple myeloma patiens regardless of treatement regimen used. Haematologica, 2014, p. 631-631.
Labels
Clinical biochemistry Nuclear medicine Nutritive therapistArticle was published in
Clinical Biochemistry and Metabolism
2017 Issue 1
Most read in this issue
- Mild Hyperhomocysteinemias From Deficiency of MTHFR (C677T and C1298A) in Adults and Adolescents Attending Metabolic Unit: Is There Any Necessity for Their Differentiation and Treatment?
- Intoxication with ethylene glycol and falsely increased plasma lactate concentration
- Nutrition and metabolism of the bone
- Relationship between cold water swimming and increased cardiac markers: A pilot study