Analysis of the relationship of heavy/light chain pairs of immunoglobulin (Hevylite™) to the results of gel electrophoresis and nefelometric examination of serum proteins at the time of multiple myeloma diagnosis
Authors:
Vlastimil Ščudla 1,2; Pavel Lochman 3; Tomáš Pika 2; Jana Zapletalová 4; Jiří Minařík 2; Jaroslav Bačovský 2
Authors place of work:
III. interní klinika – nefrologická, revmatologická a endokrinologická LF UP a FN, Olomouc
1; Hemato-onkologická klinika FN a LF UP, Olomouc
2; Oddělení klinické biochemie FN, Olomouc
3; Ústav lékařské biofyziky LF UP, Olomouc
4
Published in the journal:
Čas. Lék. čes. 2015; 154: 292-302
Category:
Original Article
Summary
Background:
The diagnostics and treatment of multiple myeloma (MM) requires precise analysis of serum immunoglobulins, which might be limited by the sensitivity of standard examination methods. Hevylite™ method enables quantitative analysis of heavy/light chain pairs (HLC) of normal and tumor IgG and IgA immunoglobulin and their ratio (HLC-r). The aim of the study was to assess the contribution of Hevylite™ method in the diagnostics of MM in comparison with nephelometry (NEF), standard protein electrophoresis (SPE), immunofixation electrophoresis (IFE) and the examination of serum free light chains (FLC) of immunoglobulin using Freelite™ test and heavy/light chain pairs of immunoglobulin (HLC) using Hevylite™.
Methods:
Using the methods Hevylite™, NEF, SPE, IFE and Freelite™, we examined a cohort of 134 individuals fulfilling the International Myeloma Working Group (IMWG) criteria. 96 patients were of IgG and 38 of IgA type.
Results:
The levels of HLC-kappa (K) and HLC-lambda (L), as well as HLC-r were independent of age and gender. Abnormal HLC levels were present in 84–100%, pathological HLC-r was in 92–100% cases based on MIg isotype. We found strong positive correlation between IgG and IgA (NEF) and the sum of HLC IgG-K + IgG-L (Hevylite™) (r = 0.80, p < 0.0001) and HLC IgA-K + IgA-L (r = 0.75, p < 0.0001). Very strong positive correlation was between the concentration of MIg (SPE) and the levels of HLC (Hevylite™) in IgG-K (r = 0.73), IgG-L (r = 0.76), IgA-K (r = 0.70) and IgA-L (r = 0.89), p < 0,0001. Systematic difference between Hevylite™ vs. MIg (SPE) was confirmed by Bland-Altmann test in the case of HLC IgA-K and IgA-L (not HLC IgG-K and IgG-L), and in the correlation of HLC with IgG and IgA (NEF). The most significant correlation between SPE (patients with < 15 g/L) vs. Hevylite™ was found within the analysis of HLC IgG-K+ IgA-K (r = 0.85, p < 0.0001), and in the whole cohort of MM patients, i.e. IgG + IgA-kappa and lambda (r = 0.76, p < 0.0001), confirmed by Bland-Altmann test. Tight positive correlation was between HLC-r and index of monoclonality FLC-K/L in MM of IgG and IgA type MM (p < 0.0001).
Conclusion:
Hevylite™ method, especially the assessment of HLC-r of IgA type MM is more sensitive in comparison with SPE evaluated by NEF, and increases the diagnostic sensitivity and the extent of tumor mass examination. Despite its limitation in the case of high levels of IgG type MIg, Hevylite™ technique has a promising potential to enrich the standard analytic tools as it enables to assess the concentration and ratio of the levels of both tumor and physiological immunoglobulins e.g. depth of immunoparesis, valid especially in MM with low levels of MIg.
Keywords:
multiple myeloma – monoclonal immunoglobulin – levels of light/heavy chain pairs of immunoglobulin – HLC-kappa/HLC-lambda ratio – Hevylite™ – serum protein electrophoresis – immunofixation electrophoresis – free light chains of immunoglobulin – Freelite™
Zdroje
1. Bradwell AR. Analysis of immunoglobulin heavy chain/light chain pairs (Hevylite™). In: Bradwell AR. Serum free light chain analysis (plus Hevylite). 6th edit. Birmingham: The Binding Site Ltd 2010: 301–320.
2. Bradwell AR, Harding SJ, Fourrier NJ, et al. Assessment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios. Clin Chemistry 2009; 55: 1646–1655.
3. 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; 27: 213–219.
4. Ščudla V, Pika T, Heřmanová Z. Hevylite – nová analytická metoda v diagnostice a hodnocení průběhu monoklonálních gamapatií. Klin Biochem Metab 2010; 18: 62–68.
5. 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: 749–757.
6. Bradwell A, Harding S, Fourrier N, et al. Prognostic utility of intact immunoglobulin Ig´kappa/Ig´lambda ratios in multiple myeloma patients. Leukemia 2013; 27: 202–207.
7. Hájek R, Adam Z, Ščudla V, et al. Souhrn doporučení CMG 2012 „Diagnostika a léčba mnohočetného myelomu“. Transfuze Hematol 2012; 18: 5–89.
8. Katzmann JA, Kyle RA, Benson J, et al. Screening panels for detection of monoclonal gammopathies. Clin Chemistry 2009; 55: 1517 –1522.
9. Vávrová J. Stanovení volných lehkých řetězců a Hevylite™ u monoklonálních gamapatií. In Maisnar V, Tichý M, et al. Monoklonální imunoglobuliny – výskyt, význam a možnosti jejich průkazu. 1. vyd. Hradec Králové: Nucleus 2012: 55 –60.
10. Wang H, Gao C, Xu L, et al. Laboratory characterisations on 2007 cases of monoclonal gammopathies in East China. Cell Moll Immunol 2008; 5: 293–298.
11. Avet-Loiseau H, Harousseau JL, Moreau P, et al. Heavy/light chain specific immunoglobulin ratios at presentation are prognostic for progression free survival in the IFM 2005-01 Myeloma trial. Blood 2009; 114: 1818.
12. Keren DF. Heavy/light-chain analysis of monoclonal gammopathies. Clin Chemistry 2009; 55: 1606 –1608.
13. 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 Biochemistry 2013; 46: 79–84.
14. Legg A, Harding S, Hughes RG, et al. Serum free light chain and Hevylite analysis in the diagnosis, monitoring and prognosis of B cell disorders. Klin Biochem Metab 2010; 18: 56–61.
15. Avet-Loiseau H, Mirbahai L, Mathiot C, et al. Nephelometric assays Ig´kappa and Ig´lambda used for diagnosing and monitoring multiple myeloma. Haematologica 2011; 96: 393a.
16. Koulieris E, Panayiotidis P, Harding SJ, et al. Ratio of involved/unilvolved immunoglobulin quantification by Hevylite™ assay: clinical and prognostic impact in multiple myeloma. Experimental Hematol § Oncology 2012; 1: 9. enhoonline.org/content/1/1/9
17. Pika T, Heřmanová Z, Lochman P, et al. Systém HevyLite™ u IgA monoklonálních gamapatií – první zkušenosti. Klin Biochem Metab 2011; 19: 86 –91.
18. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol 2005; 23: 3412–3420.
19. Donato LJ, Zeldenrust SR, Murray DL, et al. A 71-year-old woman with multiple myeloma status after stem cell transplantation. Clin Chemistry 2011; 57: 1645–1649.
20. 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: 157–163.
21. Drayson M, Berlanga O, Plant T, et al. Immunoglobulin heavy/light chain measurements during monitoring provide prognostic information of relapse after therapy in multiple myeloma patients. Blood 2012; 120: 3964a.
22. Kraj M, Kruk B, Poglod R, et al. Evaluation of IgG, IgA and IgM monoclonal and biclonal gammopathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios – Hevylite assay versus immunofixation. Acta Haematologica Polonica 2011; 42: 257–271.
23. Koulieris E, Maltezas D, Eytychia N, et al. Impact of novel M-component based biomarkers on to progression free survival after treatment in intact immunoglobulin multiple myeloma. Blood 2012; 120: 21.
24. Katzmann JA, Rajkumar SV. A windows into immunoglobulin quantitation and plasma cell disease: antigen epitopes defined by the junction of immunoglobulin heavy and light chains. Leukemia 2013; 27: 1–2.
25. Fernández de Larrea C, Tovar N, Cibeira MT, et al. Emergence of oligoclonal bands in patients with multiple myeloma in complete remission after induction therapy: association with the use of novel agents. Haematologica 2011; 96: 171–173.
26. Katzmann JA, Clark R, Kyle RA, et al. Supression of uninvolved immunoglobulins defined by heavy/light chain pair supression is a risk factor for progression of MGUS. Leukemia 2013; 27: 208–212.
27. Leibson PJ, Loken MR, Panem S, et al. Clonal evolution of myeloma cells leeds to quantitative changes in immunoglobulin secretion and surface antigen expression. Proc Natl Acad Sci ISA 1979; 76: 2937 –2941.
28. Mirbahai L, Young P, Harding S, et al. Serum free light chain (FLC) and heavy/light chain (HLC) assays provide sensitive quantitative methods for monitoring IgA multiple myeloma patients. Haematologica 2012; 97: 604.
29. Tovar N, Fernandez de Larrea C, Elena M, et al. Prognostic impact of serum immunoglobulin heavy/light chain ratio in patients with multiple myeloma in complete remission after autologous stem cell transplantation. Biol Blood Marrow Transplant 2012; 18: 1076–1107
30. Lakomy D, Lemaire –Ewing S, Lafon I, et al. IgA heavy/light chain analysis – a new marker for the diagnosis and monitoring of myeloma patients. Haematologica 2012; 97: 590.
31. Olivero B, Robillard N, Wuilleme S, et al. Heavy/light chain assay, potential new tool in minimal residual disease assessment. A biological study from IFM 2008 trial. Haematologica 2011; 96: 79a.
32. Bhutani M, Landgren O, Korde N. Serum heavy-light chains (HLC) and free light chains (FLC) as predictors for early CR in newly diagnosed myeloma patients treated with carfilzomib, lenalidomide and dexamethasone (CRd). Blood 2013; 122: 762a.
33. Murillo-Florez I, Andrade-Campos M, Montes-Limon A, et al. Predictive value of light and heavy chain analysis in multiple myeloma patients treated with bortezomib. Haematologica 2013; 98: 1519a.
34. Wechalekar A, Harding S, Lachmann H, et al. Serum immunoglobulin heavy/light chain ratios (Hevylite) in patients with systemic AL amyloidosis. Amyloid 2010; 17: 186.
35. Espino M, Medina S, Blanchard MJ, et al. Involved/unilvolved immunoglobulin ratio identifies monoclonal gammopathy of undetermined significance patients at high risk of progression to multiple myeloma. Brit J Haematol 2013: doi:10.1111/bjh.12679
36. Jardin F, Delfau –Larue MH, Molina TJ, et al. Immunoglobulin heavy/light chain pair measurement is associated with survival in diffuse large B-cell lymphoma. Leukemia § Lymphoma; doi:10.3109/10428194.2013.767456
37. Leleu X, Koulieris E, Maltezas D, et al. Novel M-component based biomarkers in Waldenström´s macroglobulinemia. Clin lymphoma, Myeloma § Leukemia 2011; 11: 164–167.
38. 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 TM u MGUS. Klin Biochem Metab 2012; 20; 63–71.
Štítky
Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental HygienistČlánok vyšiel v časopise
Journal of Czech Physicians
- Metamizole at a Glance and in Practice – Effective Non-Opioid Analgesic for All Ages
- Advances in the Treatment of Myasthenia Gravis on the Horizon
- Metamizole vs. Tramadol in Postoperative Analgesia
- Spasmolytic Effect of Metamizole
- What Effect Can Be Expected from Limosilactobacillus reuteri in Mucositis and Peri-Implantitis?
Najčítanejšie v tomto čísle
- Mountain sickness
- Non-cardiogenic pulmonary edema, acute respiratory distress syndrome
- Chronic heart failure
- Analysis of the relationship of heavy/light chain pairs of immunoglobulin (Hevylite™) to the results of gel electrophoresis and nefelometric examination of serum proteins at the time of multiple myeloma diagnosis