Terapevticheskii arkhivTerapevticheskii arkhivТерапевтический архив0040-36602309-5342LLC Obyedinennaya Redaktsiya10485510.26442/00403660.2022.01.201326LectureЛекцияReview ArticleDetection of paraprotein in plasma cell tumorsОпределение парапротеина при плазмоклеточных опухоляхhttps://orcid.org/0000-0001-5440-4340RekhtinaIrina G.РехтинаИрина Германовна
Russian Federation

д-р мед. наук, зав. отд-нием химиотерапии плазмоклеточных дискразий

rekhtina.i@blood.ruhttps://orcid.org/0000-0002-4966-8146MendeleevaLarisa P.МенделееваЛариса Павловна
Russian Federation

д-р мед. наук, проф., рук. управления по научной и образовательной работе, зав. отд. химиотерапии парапротеинемических гемобластозов

rekhtina.i@blood.ruhttps://orcid.org/0000-0002-1903-2446SobolevaNatalia P.СоболеваНаталья Павловна
Russian Federation

врач клинической лабораторной диагностики централизованной клинико-диагностической лаб.

rekhtina.i@blood.ruhttps://orcid.org/0000-0001-5256-7066DubinaIrina A.ДубинаИрина Александровна
Russian Federation

врач клинической лабораторной диагностики

rekhtina.i@blood.ruhttps://orcid.org/0000-0001-9630-257XPervakovaMargarita Iu.ПерваковаМаргарита Юрьевна
Russian Federation

врач клинической лабораторной диагностики

rekhtina.i@blood.ruhttps://orcid.org/0000-0002-4998-3699LapinSergey V.ЛапинСергей Владимирович
Russian Federation

канд. мед. наук, зав. лаб. диагностики аутоиммунных заболеваний

rekhtina.i@blood.ruNational Medical Research Center for HematologyФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава РоссииPavlov First Saint Petersburg State Medical UniversityФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России150120229411351441403202214032022Copyright ©; 2022, Consilium MedicumCopyright ©; 2022, ООО "Консилиум Медикум"2022Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://ter-arkhiv.ru/0040-3660/article/view/104855

Paraprotein is a laboratory biomarker of plasma cell tumors and other lymphoproliferative diseases. Its determination is necessary for diagnosing, monitoring and assessment of therapy effectiveness. The lecture presents the main methods of qualitative and quantative analysis of monoclonal proteins: gel electrophoresis, capillary electrophoresis, immunofixation and nephelometry features, possibilities and limitations are reviewed. The main sources of errors and artifacts during these studies are considered. Also the difficulties in the diagnosis and interpretation of the results of serum and urine tests are highlighted.

Парапротеин – лабораторный биомаркер плазмоклеточных опухолей и других лимфопролиферативных заболеваний, определение которого необходимо для диагностики, оценки эффективности проводимой терапии и мониторинга. В данной лекции приведены основные методы качественного и количественного анализа моноклональных белков: изложены особенности, возможности и ограничения гель- электрофореза, капиллярного электрофореза, иммунофиксации и нефелометрии. Рассмотрены основные источники ошибок и артефактов при выполнении этих исследований. Обращено внимание на трудности в диагностике и интерпретации результатов исследования сыворотки и мочи.

paraproteinmultiple myelomaplasma cell diseaseпарапротеинмножественная миеломаплазмоклеточное заболеваниеWHO classification of tumours oh haematopoetic and lymphoid tissues. Ed. by Swerdlov SH, Campo E, Harris NL, et al. Revised 4th ed.Bradwell AR. Serum free light chain analysis plus hevylite. 7th ed. UK (Birmingham): The Binding Site Group, 2015.Katzmann JA. Screening panels for monoclonal gammopathies: time to change. Clin Biochem Rev. 2009;30:105-11.García-García P, Enciso-Alvarez K, Diaz-Espada F, et al. Biclonal gammopathies: Retrospective study of 47 patients. Rev Clin Esp. 2015;215(1):18-24. DOI:10.1016/j.rce.2014.07.003Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma. Lancet Oncol. 2016;17(8):e328-46. DOI:10.1016/S1470-2045(16)30206-6Palladini G, Dispenzieri A, Gertz MA, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012;30(36):4541-9. DOI:10.1200/JCO.2011.37.7614Keren DF, Alexanian R, Goeken JA, et al. Guidelines for clinical and laboratory evaluation patients with monoclonal gammopathies. Arch Pathol Lab Med. 1999;123(2):106-7. DOI:10.5858/1999-123-0106-GFCALETate J, Caldwell G, Daly J, et al. Recommendations for standardized reporting of protein electrophoresis in Australia and New Zealand. Ann Clin Biochem. 2012;49:242-56. DOI:10.1258/acb.2011.011158Keren DF, Schroeder L. Challenges of measuring monoclonal proteins in serum. Clin Chem Lab Med. 2016;54(6):947-61. DOI:10.1515/cclm-2015-0862Keren D. Protein Electrophoresis in Clinical Diagnosis. London, 2003.Sørrig R, Klausen TW, Salomo M, et al. Immunoparesis in newly diagnosed Multiple Myeloma patients: Effects on overall survival and progression free survival in the Danish population. PLoS One. 2017;12(12):e0188988. DOI:10.1371/journal.pone.0188988Fujisawa M, Seike K, Fukumoto K, et al. Oligoclonal bands in patients with multiple myeloma: Its emergence per se could not be translated to improved survival. Cancer Sci. 2014;105(11):1442-6. DOI:10.1111/cas.12527Willrich 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-2015-0580Murray 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.2009.124461Bergón E, Miravalles E. Estimation of serum M-protein concentration from polyclonal immunoglobulins: an alternative to serum protein electrophoresis and standard immunochemical procedures. Clin Chem Lab Med. 2008;46(8):1156-62. DOI:10.1515/CCLM.2008.232Ramakrishnan N, Jialal I. Bence-Jones Protein. StatPearls: Treasure Island (FL), 2019.Csako G. Immunofixation Electrophoresis for Identification of Proteins and Specific Antibodies. In: Methods in molecular biology (Clifton, NJ). United States, 2019; p. 177-201.Booth RA, McCudden CR, Balion CM, et al. Candidate recommendations for protein electrophoresis reporting from the Canadian Society of Clinical Chemists Monoclonal Gammopathy Working Group. Clin Biochem. 2018;51:10-20. DOI:10.1016/j.clinbiochem.2017.10.013Waldmann TA, Strober W, Mogielnicki RP. The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia. J Clin Invest. 1972;51:2162-74. DOI:10.1172/JCI107023Solomon A. Light chains of human immunoglobulins. Meth Enzymol. 1985;116:1-121. DOI:10.1016/S0076-6879(85)16008-8Katzmann JA, Clark RJ, Abraham RS, et al. Serum reference intervals and diagnostic ranges for free k and free l immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002;4(9):1437-44.Drayson M, Begum G, Basu S, et al. Effects of paraprotein heavy and light chain types and free light chain load on survival in myeloma: an analysis of patients receiving conventional-dose chemotherapy in Medical Research Council UK multiple myeloma trials. Blood. 2006;108(6):2013-9. DOI:10.1182/blood-2006-03-008953Bradwell AR, Carr-Smith HD, Mead GP, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem. 2001;47:673-80.Dispenzieri A, Kyle R, Merlini G, et al; International myeloma working group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009;23:215-24. DOI:10.1038/leu.2008.307Schild C, Wermuth B, Trapp-Chiappini D, et al. Reliability of M protein quantification: comparison of two peak integration methods on Capillarys 2. Clin Chem Lab Med. 2008;46(6):876-7. DOI:10.1515/CCLM.2008.146Kumar SK, Dispenzieri A, Lacy MQ, et al. Changes in serum-free light chain rather than intact monoclonal immunoglobulin levels predicts outcome following therapy in primary amyloidosis. Am J Hematol. 2011;86(3):251-5. DOI:10.1002/ajh.21948Comenzo RL, Reece D, Palladini G, et al. Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis. Leukemia. 2012;26(11):2317-25. DOI:10.1038/leu.2012.100Manwani R, Cohen O, Sharpley F, et al. A prospective observational study of 915 patients with systemic AL amyloidosis treated with upfront bortezomib. Blood. 2019;134(25):2271-80. DOI:10.1182/blood.2019000834Katzmann JA, Snyder MR, Rajkumar SV, et al. Long-term biological variation of serum protein electrophoresis M-spike, urine M-spike, and monoclonal serum free light chain quantification: implications for monitoring monoclonal gammopathies. Clin Chem. 2011;57:1687-92. DOI:10.1373/clinchem.2011.171314Kühnemund A, Liebisch P, Bauchmüller K, et al. Light-chain escape-multiple myeloma'- an escape phenomenon from plateau phase: report of the largest patient series using LC-monitoring. J Cancer Res Clin Oncol. 2009;135(3):477-84. DOI:10.1007/s00432-008-0470-7Hutchison CA, Harding S, Hewins P, et al. Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2008;3:1684-90. DOI:10.2215/CJN.02290508Рехтина И.Г., Менделеева Л.П., Соболева Н.П. Трудности в оценке гематологического ответа у больных множественной миеломой с диализзависимой почечной недостаточностью. Терапевтический архив. 2019;91(7):70-4 [Rekhtina IG, Mendeleeva LP, Soboleva NP. Difficulties evaluating hematological response in patients with multiple myeloma and dialysis-dependent renal impairment. Terapevticheskii Arkhiv (Ter. Arkh.). 2019;91(7):70-4 (in Russian)]. DOI:10.26442/00403660.2019.07.000215Dimopoulos M, Sonneveld P, Leung N, et al. International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol. 2016;34:1544-57. DOI:10.1200/JCO.2015.65.0044Marron ТU, Ramanathan L, Chari A. Diagnostic utility of measuring free light chains in the cerebrospinal fluid of patients with multiple myeloma. Clin Lymphoma Myeloma Leuk. 2015;15(6):e127-31. DOI:10.1016/j.clml.2015.02.028