Detection of paraprotein in plasma cell tumors

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Abstract

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.

About the authors

Irina G. Rekhtina

National Medical Research Center for Hematology

Author for correspondence.
Email: rekhtina.i@blood.ru
ORCID iD: 0000-0001-5440-4340

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

Russian Federation, Moscow

Larisa P. Mendeleeva

National Medical Research Center for Hematology

Email: rekhtina.i@blood.ru
ORCID iD: 0000-0002-4966-8146

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

Russian Federation, Moscow

Natalia P. Soboleva

National Medical Research Center for Hematology

Email: rekhtina.i@blood.ru
ORCID iD: 0000-0002-1903-2446

врач клинической лабораторной диагностики централизованной клинико-диагностической лаб.

Russian Federation, Moscow

Irina A. Dubina

Pavlov First Saint Petersburg State Medical University

Email: rekhtina.i@blood.ru
ORCID iD: 0000-0001-5256-7066

врач клинической лабораторной диагностики

Russian Federation, Saint Petersburg

Margarita Iu. Pervakova

Pavlov First Saint Petersburg State Medical University

Email: rekhtina.i@blood.ru
ORCID iD: 0000-0001-9630-257X

врач клинической лабораторной диагностики

Russian Federation, Saint Petersburg

Sergey V. Lapin

Pavlov First Saint Petersburg State Medical University

Email: rekhtina.i@blood.ru
ORCID iD: 0000-0002-4998-3699

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

Russian Federation, Saint Petersburg

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Supplementary files

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2. Fig. 1. Serum electrophoresis densitograms with normal polyclonal immune response (a), monoclonal Ig synthesis without immunoparesis (b) and with immunoparesis (c).

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3. Fig. 2. An example of immunofixation of blood serum: a – polyvalent synthesis of all types of chains; b – monovalent synthesis of γ- and κ-chains.

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4. Fig. 3. Sorption of the paraprotein on the gel: a – identification of the paraprotein composition is impossible, precipitation bands are observed with all antisera; b – thanks to the preliminary treatment of blood serum with 2-mercaptoethanol, the composition of the IgM/κ paraprotein was determined.

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5. Fig. 4. Artifact during immunofixation of blood serum: a – identification of the light chain is difficult, since with the dilution of the sample used (1:5), the center of the κ-precipitate is washed out, which is due to an excess of antigen; b – a stronger dilution of the sample (1:10) allows eliminating the artifact and identifying the light chain.

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6. Fig. 5. The presence of several M-peaks on the densitogram: a – biclonal gammopathy: 2 monoclonal peaks were detected (left), immunofixation (right) showed that they have a different composition; b – intraclonal heterogeneity: 2 monoclonal peaks were detected (left), immunofixation (right) showed that they are represented by whole Ig and free light chains.

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7. Рис. 6. Пример денситограммы (а) сыворотки крови больного нефротическим синдромом с расчетом количественного содержания отдельных фракций и указанием наблюдаемых изменений (b).

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8. Fig. 7. An example of urine immunofixation. The sample revealed Bence-Jones protein represented by light chains λ.

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9. Fig. 8. The dependence of the concentration of the monoclonal component on the method of its isolation on the densitometric curve: a – the amount of paraprotein measured by the "full" peak method is 42.92 g/l; b – when using the "truncated" peak method, the concentration is 30.92 g/l.

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10. Fig. 9. An example of a diagnostic conclusion of paraproteinemia by electrophoresis and immunofixation.

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