Free light chains of immunoglobulins in the diagnosis and prognosis of multiple myeloma
- Authors: Lyubimova N.V.1, Timofeev Y.S.1, Votyakova O.M.1, Kushlinskii N.E.1
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Affiliations:
- N.N. Blokhin Russian Cancer Research Center
- Issue: Vol 45, No 2 (2017)
- Pages: 102-108
- Section: ARTICLES
- URL: https://almclinmed.ru/jour/article/view/521
- DOI: https://doi.org/10.18786/2072-0505-2017-45-2-102-108
- ID: 521
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Full Text
Abstract
Background: Analysis of free light chains of immunoglobulins (FLC) in the serum is an effective method in the diagnosis of multiple myeloma. Plasma cells produce two types of FLC: κand λ-FLC. FLC, which are not incorporated into monoclonal intact immunoglobulins, are released into circulation, and then are filtered and reabsorbed in kidneys depending on their molecular weight. Circulating FLC commonly form homodimers, known as Bence-Jones protein, which is a biomarker of Bence-Jones multiple myeloma. According to the international guidelines, the ratio κ/λ FLC is an important diagnostic criterion of multiple myeloma. Aim: To evaluate the diagnostic and prognostic value of serum FLC in multiple myeloma patients. Materials and methods: We examined 118 patients with multiple myeloma, admitted to the Department of Hemoblastosis Chemotherapy of N.N. Blokhin Russian Cancer Research Center from 2010 to 2016, and 68 healthy men and women. Serum concentrations of FLC were measured with an immunoturbidimetric method using the test-system Freelite Human Lambda and Freelite Human Kappa (Binding Site Inc.). Results: The levels of monoclonal κor λ-FLC in patients with G-, A-myeloma and Bence-Jones multiple myeloma were significantly higher than those in the control group (p < 0.005). The diagnostic sensitivity of quantification of FLC and their ratio was 87.3% and 89.8%, and in combination with the use of immune electrophoresis it was close to 100%. Analysis of progression free survival and overall survival showed significant differences (p < 0.04) between the groups of patients according their κ/λ FLC ratio. The basal value of κ/λ FLC ratio of less than 0.04 and more than 140 was a predictor of unfavorable outcome. Conclusion: The inclusion of the determination of serum FLC into the assessment plan of patients with suspected monoclonal gammapathy makes it possible to increase diagnostic sensitivity of the available methods for paraprotein determination, as well as to monitor patients with non-secreting multiple myeloma. FLC analysis in multiple myeloma patients acquires special significance in the prognosis of remission, since the antitumor response based on their measurement is seen earlier than that based on the results of standard immunochemistry studies.
About the authors
N. V. Lyubimova
N.N. Blokhin Russian Cancer Research Center
Author for correspondence.
Email: biochimia@mtu-net.ru
Lyubimova Nina V. – Doctor of Biol. Sci., Professor, Leading Researcher, Laboratory of Clinical Biochemistry
24 Kashirskoe shosse, Moscow, 115478
РоссияYu. S. Timofeev
N.N. Blokhin Russian Cancer Research Center
Email: fake@neicon.ru
Timofeev Yuriy S. – MD, Physician, Laboratory of Clinical Biochemistry
24 Kashirskoe shosse, Moscow, 115478
РоссияO. M. Votyakova
N.N. Blokhin Russian Cancer Research Center
Email: fake@neicon.ru
Votyakova Olga M. – MD, PhD, Senior Researcher, Department of Hemoblastosis Chemotherapy
24 Kashirskoe shosse, Moscow, 115478
РоссияN. E. Kushlinskii
N.N. Blokhin Russian Cancer Research Center
Email: fake@neicon.ru
Kushlinskii Nikolay E. – MD, PhD, Professor, Member-Correspondent of Russian Academy of Sciences, Head of Laboratory of Clinical Biochemistry
24 Kashirskoe shosse, Moscow, 115478
РоссияReferences
- Willrich MA, Katzmann JA. Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias. Clin Chem Lab Med. 2016;54(6): 907–19. doi: 10.1515/cclm-2015-0580.
- Murray DL, Ryu E, Snyder MR, Katzmann JA. Quantitation of serum monoclonal proteins: relationship between agarose gel electrophoresis and immunonephelometry. Clin Chem. 2009;55(8):1523–9. doi: 10.1373/clinchem.2009.124461.
- Misra A, Mishra J, Chandramohan J, Sharma A, Raina V, Kumar R, Soni S, Chopra A. Old but still relevant: high resolution electrophoresis and immunofixation in multiple myeloma. Indian J Hematol Blood Transfus. 2016;32(1):10–7. doi: 10.1007/s12288-015-0605-3.
- Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, Palumbo A, Jagannath S, Blade J, Lonial S, Dimopoulos M, Comenzo R, Einsele H, Barlogie B, Anderson K, Gertz M, Harousseau JL, Attal M, Tosi P, Sonneveld P, Boccadoro M, Morgan G, Richardson P, Sezer O, Mateos MV, Cavo M, Joshua D, Turesson I, Chen W, Shimizu K, Powles R, Rajkumar SV, Durie BG; International Myeloma Working Group. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009;23(2):215–24. doi: 10.1038/leu.2008.307.
- Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–48. doi: 10.1016/S1470-2045(14)70442-5.
- Rajkumar SV. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91(7):719–34. doi: 10.1002/ajh.24402.
- Bradwell AR. Serum free light chain measurements move to center stage. Clin Chem. 2005;51(5):805–7. doi: 10.1373/clinchem.2005.048017.
- Bradwell AR, Harding SJ, Fourrier NJ, Wallis GL, Drayson MT, Carr-Smith HD, Mead GP. Assessment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios. Clin Chem. 2009;55(9):1646–55. doi: 10.1373/clinchem.2009.123828.
- van Rhee F, Bolejack V, Hollmig K, Pineda-Roman M, Anaissie E, Epstein J, Shaughnessy JD Jr, Zangari M, Tricot G, Mohiuddin A, Alsayed Y, Woods G, Crowley J, Barlogie B. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood. 2007;110(3):827–32. doi: 10.1182/blood-2007-01-067728.
- Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, Drew R. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem. 2001;47(4):673–80.
- Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002;48(9):1437–44.
- Snozek CL, Katzmann JA, Kyle RA, Dispenzieri A, Larson DR, Therneau TM, Melton LJ 3rd, Kumar S, Greipp PR, Clark RJ, Rajkumar SV. Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia. 2008;22(10):1933–7. doi: 10.1038/leu.2008.171.
- Kyrtsonis MC, Maltezas D, Tzenou T, Koulieris E, Bradwell AR. Staging systems and prognostic factors as a guide to therapeutic decisions in multiple myeloma. Semin Hematol. 2009;46(2):110–7. doi: 10.1053/j.seminhematol.2009.02.004.
- Bradwell A, Harding S, Fourrier N, Mathiot C, Attal M, Moreau P, Harousseau JL, AvetLoiseau H. Prognostic utility of intact immunoglobulin Ig'κ/Ig'λ ratios in multiple myeloma patients. Leukemia. 2013;27(1):202– 7. doi: 10.1038/leu.2012.159.
- Любимова НВ, Турко ТА, Вотякова ОМ, Кушлинский НЕ. Свободные легкие цепи иммуноглобулинов в сыворотке крови больных моноклональными гаммапатиями. Бюллетень экспериментальной биологии и медицины. 2012;153(2):217–22.
- Турко ТА, Любимова НВ, Агеева ТВ, Вотякова ОМ. Свободные легкие цепи иммуноглобулинов при множественной миеломе. Клиническая лабораторная диагностика. 2010;(9):29–29a.
- Митина ТА, Голенков АК, Яздовский ВВ, Караулов АВ, Москалец ОВ, Клинушкина ЕФ, Катаева ЕВ, Трифонова ЕВ, Луцкая ТД, Дудина ГА, Высоцкая ЛЛ, Черных ЮБ, Захаров СГ, Белоусов КА, Фомин АМ, Когарко ИН. Кинетика свободных легких цепей иммуноглобулинов сыворотки крови у пациентов с множественной миеломой в процессе проведения курсов химиотерапии, включающих леналидомид. Иммунология. 2014;35(6):329–32.
- Голенков АК, Трифонова ЕВ, Митина ТА, Москалец ОВ, Белоусов КА, Катаева ЕВ, Кедров АВ, Когарко ИН, Когарко БС, Яздовский ВВ, Караулов АВ. Значение исследования свободных легких цепей в спинномозговой жидкости при множественной миеломе, осложненной миелорадикулопатией. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2016;9(3):345–6.
- Larsen JT, Kumar SK, Dispenzieri A, Kyle RA, Katzmann JA, Rajkumar SV. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia. 2013;27(4):941–6. doi: 10.1038/leu.2012.296.
- Sigurdardottir EE, Turesson I, Lund SH, Lindqvist EK, Mailankody S, Korde N, Björkholm M, Landgren O, Kristinsson SY. The Role of Diagnosis and Clinical Follow-up of Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma. JAMA Oncol. 2015;1(2):168–74. doi: 10.1001/jamaoncol.2015.23.