Clinical and laboratory aspects of biclonal gammopathy of undetermined significance - BGUS

Česká verzia

Authors: T. Pika ¹; P. Lochman ²; V. Maisnar ³; M. Tichý ⁴; J. Minařík ¹; R. Hájek ⁵; V. Ščudla ¹
Authors place of work: III. interní klinika – nefrologická, revmatologická, endokrinologická, LF UP a FN Olomouc ¹; Oddělení klinické biochemie, FN Olomouc ²; IV. interní hematologická klinika, LF UK a FN Hradec Králové ³; Ústav klinické biochemie a diagnostiky, LF UK a FN Hradec Králové ⁴; Ústav klinické hematologie, LF OU a FN Ostrava ⁵
Published in the journal: Klin. Biochem. Metab., 21 (42), 2013, No. 2, p. 83-87

Summary

Introduction:
Biclonal gammopathy of undetermined significance (BGUS) is a less frequent disease characterized by the presence of two monoclonal gradients and a relatively favourable biological development.

Objective:
The objective was to assess potential benefits and/or limitations of laboratory parameters typically used with monoclonal gammopathy of undetermined significance (MGUS) when applied to a group of BGUS patients.

Methods:
The analysed batch comprised 18 serum samples from BGUS patients (9x IgG–IgA, 7x IgG–IgM a 2x IgG–IgG type). The assays were performed with a SPA Plus turbidimeter. Serum levels of polyclonal immunoglobulins, free light immunoglobulin chains (FreeLite™), and pairs of heavy/light immunoglobulin chains (HevyLite™) were assayed.

Results and conclusion:
The results of the pilot analyses confirm that a significant portion of BGUS patients exhibits changes of certain parameters typically applied to the stratification and monitoring of MGUS patients, particularly when the light chains in both molecules of monoclonal immunoglobulins differ. The analysis of heavy/light immunoglobulin chain pairs (HLC) appears very promising, indicating the possibility of an isotype suppression of the alternative pair affecting the HLC index. It is apparent, however, that the isolation and analysis of cell clones on a molecular and cytogenetic level will be essential for BGUS prognosis in clinical practice.

Key words:
biclonal gammopathy, prognostic factors, diagnostics.

Zdroje

1. Špička, I. et al. Mnohočetný myelom a další mono-klonální gamapatie. Galén 2005, Praha, p. 39-60.

2. The International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Brit J Haematol,2003, 121, p. 749-757.

3. Kyle, R. A., Therneau, T. M., Rajkumar, S. V. et al. Prevalence of monoclonal gammopathy of undetermined significance. N. Engl. J. Med., 2006, 354, p. 1362-9.

4. Ščudla, V., Pika, T. Monoklonální gamapatie nejistého významu ve světle současných poznatků. Klin. Biochem. Metab., 2009, 38, p. 62-71.

5. Kyle, R. A., Therneau, T. M., Rajkumar, S. V. et al. A long-term study of prognosis in monoclonal gammopathy of undetermined sifnificance. N. Engl. J. Med., 2002, 346, p. 564-569.

6. Baldini, L., Guffanti, A., Cesana, B. M. et al. Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy. Blood. 1996, 87, 912-918.

7. Cesana, C., Klersy, C., Barbarano, L. et al. Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smolde-ring multiple myeloma. J. Clin. Oncol. 2002, 20, 1625-1634.

8. Veneri, D., Agel, H., Franchini, M. et al. Malignant evolution of monoclonal gammopathy of undetermined signifikance: analysis of 633 consecutive cases with a long term follow-up. Haematologica. 2004, 89, 876-878.

9. Sackmann, F., Pavlovsky, M. A., Corrado, C. et al. Prognostic factors in monoclonal gammopathy of undetermined significance. Haematologica. 2008, 93, 153-154.

10. Rajkumar, S. V., Kyle, R. A., Therneau, T. M. et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005, 106, 812-817.

11. Pika, T., Minařík, J., Lochman, P., Bačovský, J., Ščudla, V. Sérové hladiny volných lehkých řetězců imunoglobulinu u monoklonální gamapatie nejistého významu a jejich přínos pro stratifikaci a sledování. Transfuze. Hematol. dnes. 2011, 17, 177-181.

12. Kyle, R. A., Durie, B. G. M., Landgren, O. et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple mye-loma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010, 24, 1121-1127.

13. Katzmann, J. A., Clark, R., Dispenzieri, A. et al. Isotype-specific heavy/light chain (HLC) suppression as a predictor of myeloma development in monoclonal gammopathy of undetermined significance (MGUS). Blood 2009, 114, abstract 1788.

14. Katzmann, J. A., Clark, R., Kyle, R. A. et al. Suppression of uninvolved immunoglobulins defined by heavy/light chain pair suppression is a risk factor for progression of MGUS. Leukemia 2012, 10.1038/leu.2012.189.

15. Pika, T., Lochman, P., Klincová, M. et al. Suprese alternativního páru imunoglobulinu koreluje s mírou rizikovosti MGUS výrazněji nežli suprese hladin polyklonálních imunoglobulinů – dílčí výsledky vyšetření HevyLite™ u MGUS. Klin. Biochem. Metab. 2012, 41, 63-71.

16. Kyle, R. A., Robinson, R. A., Katzmann, J. A. The clinical aspects of biclonal gammopathies. Am. J. Med. 1981, 71, 999 – 1008.

17. Tichý, M., Vávrová, J., Maisnar, V. Zdvojené paraproteinémie. Klin. Biochem. Metab. 2011, 19, 91-92.

18. Tichý, M., Maisnar, V. Zdvojené gamapatie. In Maisnar, V., Tichý, M. et al., Monoklonální imunoglobuliny – výskyt, význam a možnosti jejich průkazu. Nucleus –HK, Hradec Králové, 2012, p. 104 – 107.

19. Mahto, M., Balakrishnan, P., Koner, B. C. et al. Rare case of biclonal gammopathy. IJCRI 2011, 2. 11-14.

20. Bradwell, A. R. Serum free light chain measurements move to center stage. Clin. Chem., 2005, 51, 5, p. 805-807.

21. Bradwell, A. R. Implementation and interpretation of free light chain assays. In Bradwell A. R, Serum free light chain analysis, 5^th edition. Birmingham, The Binding Site Ltd., 2008, p. 215 - 222.

22. Bradwell, A. R. Analysis of immunoglobulin heavy chain/light chain pairs (Hevylite™). In Bradwell A. R, Serum free light chain analysis, 6th edition. Birmingham, The Binding Site Ltd., 2010, p. 301-320.

23. 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, 1646-55.