The role of electrophoresis in the diagnosis of multiple myeloma. Archive on myeloma M gradient in the blood, what does it show?

On the eve of the study, consumables (container with adapter and test tube) must first be obtained from any laboratory department.
Please note that in The laboratory department delivers biomaterial only in a urine test tube with an olive cap (according to the collection instructions).

Bence Jones protein- a tumor marker that is used to diagnose multiple myeloma (plasma cell tumor). Bence Jones protein consists of free light chains of immunoglobulins. In healthy people, a small amount of free light chains is constantly produced, along with complete immunoglobulin molecules. Due to their small molecular weight and neutral charge, they are filtered into the primary urine through the glomerular basement membrane, then reabsorbed and metabolized in the proximal tubules without ending up in the final urine. In monoclonal gammopathies, the production of abnormal immunoglobulins by the malignant clone of plasma cells is observed. This leads to an excess of free light chains in the primary urine and the appearance of Bence Jones protein in the final urine.

The synthesis of monoclonal immunoglobulins is accompanied by the formation of a variable amount of light chains. About 20% of myeloma cases are characterized by the production of exclusively monoclonal light chains (light chain disease).

Determination of Bence Jones protein in urine reflects kidney damage - tubular atrophy, severe sclerosis of the renal interstitium. Damage is enhanced by predisposing factors (dehydration, hypercalcemia, use of radiocontrast agents, certain medications), which can lead to renal failure.

Compound:
  • Percentage of albumin in urine
  • Screening for urinary paraprotein (Bence Jones protein) with polyvalent antiserum
  • M-gradient in urine (Bence Jones protein), concentration
  • Determination of total protein content in urine

Paraproteins are normally absent in blood serum.

Immunoglobulinopathies, or gammopathies, comprise a large group of pathological conditions characterized by polyclonal or monoclonal hypergammaglobulinemia. Immunoglobulins consist of two heavy (H) chains (molecular weight 50,000) and two light (L) chains (molecular weight 25,000). The chains are connected by disulfide bridges and consist of structures called domains (H - of 4, L - of 2 domains). Under the action of proteolytic enzymes, Ig is divided into fragments: Fc fragment and Fab fragment. Human Ig heavy chains are represented by five structural variants, which are designated by the letters of the Greek alphabet: γ, α, μ, δ, ε. They correspond to 5 classes of Ig - G, A, M, D, E. Light chains are represented by two structurally different variants: κ (kappa) and λ (lambda), which correspond to two types of Ig of each class. In each Ig molecule, both heavy and both light chains are identical. All people normally have Igs of all classes and both types, but their relative content is not the same. The ratio of κ and λ molecules within different Ig classes is also different. Detection of disturbances in the ratios of Ig or their fragments plays a vital role in the diagnosis of monoclonal immunoglobulinopathies.

Monoclonal immunoglobulinopathy (paraproteinemia) is a syndrome expressed in the accumulation in the blood serum and/or urine of patients of Ig or their fragments that are homogeneous in all physicochemical and biological parameters. Monoclonal Ig (paraproteins, M-proteins) are a secretion product of one clone of B-lymphocytes (plasma cells), therefore they represent a pool of structurally homogeneous molecules having heavy chains of the same class (subclass), light chains of the same type and variable regions of the same structure. Monoclonal immunoglobulinopathies are usually divided into benign and malignant. In benign forms of monoclonal gammopathies, plasma cell proliferation is controlled (possibly by the immune system) so that clinical symptoms are absent. In malignant forms, uncontrolled proliferation of lymphoid or plasma cells occurs, which determines the clinical picture of the disease.

Classification of monoclonal immunoglobulinopathies

Nature of the pathology

Concentration of pathological Ig in blood serum, g/l

B-cell malignancies

Multiple myeloma, Waldenström macroglobulinemia

More than 25

Plasmacytoma (solitary - bone and extramedullary), lymphoma, chronic lymphocytic leukemia, heavy chain disease

Well below 25
B-cell benignMonoclonal gammopathies of unknown originBelow 25
Primary (Wiskott-Aldrich, DiGeorge, Nezelef syndromes, severe combined immunodeficiency)Below 25
Secondary (age-related, caused by the use of immunosuppressants, concomitant with cancer of a non-lymphoid nature (for example, colon cancer, breast cancer, prostate cancer, etc.)Below 2.5
Immunodeficiency states with an imbalance of the T and B links of the immune systemRestructuring of the immune system after red bone marrow transplantationBelow 25
Antigenic stimulation in early ontogenesis (intrauterine infection)Below 25
Homogeneous immune responseBacterial infectionsBelow 25
Autoimmune diseases such as cryoglobulinemia, SLE, rheumatoid arthritis, etc.Below 25

Immunoelectrophoresis of serum proteins makes it possible to detect monoclonal (pathological) IgA, IgM, IgG, H and L chains, and paraproteins. In conventional electrophoresis, normal Ig, heterogeneous in properties, are located in the γ zone, forming a plateau or a wide band. Monoclonal Igs, due to their homogeneity, migrate predominantly to the γ zone, occasionally to the β zone and even to the α region, where they form a high peak or a clearly demarcated band (M-gradient).

Multiple myeloma (Rustitsky-Kahler disease) is the most common paraproteinemic hemoblastosis; it is detected no less often than chronic myelo- and lymphocytic leukemia, lymphogranulomatosis and acute leukemia. The class and type of pathological Ig secreted by myeloma determines the immunochemical variant of the disease. The frequency of classes and types of pathological Igs in myeloma generally correlates with the ratio of classes and types of normal Igs in healthy people.

Along with an increase in the content of pathological Ig in the serum of patients with multiple myeloma, normal Ig is determined in a reduced concentration. The total protein content is sharply increased - up to 100 g/l. The activity of the process in G-myeloma is assessed by the number of plasma cells in the sternal punctate, the concentration of creatinine and calcium in the blood serum (their increase in calcium indicates the progression of the disease). The concentration of M protein (called Bence Jones protein in urine) serves as a criterion for assessing disease progression in A myeloma. The concentration of paraproteins in serum and urine varies during the course of the disease under the influence of therapy.

To make a diagnosis of multiple myeloma, the following criteria must be met.

Large criteria

  1. Plasmacytoma based on biopsy results.
  2. Plasmocytosis in the red bone marrow (more than 30% of cells).
  3. Monoclonal (pathological) Ig peaks on serum protein electrophoresis: greater than 35 g/L for an IgG peak or greater than 20 g/L for an IgA peak. Excretion of κ and λ chains in an amount of 1 g/day or more, detected by urine electrophoresis in a patient without amyloidosis.

Small criteria

  1. Plasmocytosis in the red bone marrow of 10-30% of cells.
  2. Peak PIg in the blood serum in an amount less than indicated above.
  3. Lytic bone lesions.
  4. The concentration of normal IgM is below 0.5 g/l, IgA is below 1 g/l or IgG is below 0.6 g/l.

To make a diagnosis of multiple myeloma, at least 1 major and 1 minor criterion or 3 minor criteria are required with the mandatory presence of the criteria given in paragraphs 1 and 2.

To determine the stage of myeloma, the standardizing Durie-Salmon system is used, which reflects the volume of the tumor lesion.

All groups of myelomas are divided into subclasses depending on the state of renal function: A - serum creatinine concentration below 2 mg% (176.8 µmol/l), B - more than 2 mg%. In multiple myeloma, a high concentration of β 2 -microglobulin in the blood serum (more than 6000 ng/ml) suggests an unfavorable prognosis, as well as high LDH activity (above 300 IU/l, reaction at 30 °C), anemia, renal failure, hypercalcemia, hypoalbuminemia and large tumor volume.

Light chain diseases (Bence Jones myeloma) account for approximately 20% of myeloma cases. In Bence-Jones myeloma, exclusively free light chains are formed, which are detected in the urine (Bence-Jones protein), in the absence of a pathological serum Ig (M-gradient).

Stages of multiple myeloma

Stage

Criteria

Tumor mass (number of cells), x10 12 /m 2

Small myeloma with the following criteria:

hemoglobin concentration in the blood is above 100 g/l;

the concentration of total calcium in the blood serum is normal (

no changes in bones on radiography or solitary plasmacytoma of bone;

low concentration of paraproteins in blood serum (IgG below 50 g/l, IgA below 30 g/l);

L-chains (Bence Jones protein) in urine less than 4 g/24 h

Intermediate myeloma (criteria are between stages I and III)

Major myeloma with one or more of the following criteria:

hemoglobin concentration in the blood is below 85 g/l;

the concentration of total calcium in the blood serum is higher than 12 mg% (3 mmol/l);

extensive skeletal damage or major fractures;

high concentration of paraproteins in blood serum (IgG more than 70 g/l, IgA more than 50 g/l);

L-chains (Bence Jones protein) in urine more than 12 g/24 hours.

Rare immunochemical variants of multiple myeloma include nonsecretory myeloma, in which paraproteins can only be found in the cytoplasm of myeloma cells, as well as diclon myeloma and M-myeloma.

Waldenström's macroglobulinemia is a chronic subleukemic leukemia of B-cell nature, morphologically represented by lymphocytes, plasma cells and all transitional forms of cells that synthesize PIgM (macroglobulin). The tumor has a low degree of malignancy. In the red bone marrow, proliferation of small basophilic lymphocytes (plasmacytoid lymphocytes) is detected, and the number of mast cells is increased. On the electropherogram of blood serum proteins, an M-gradient is detected in the zone of β- or γ-globulins; less often, the paraprotein does not migrate in the electric field, remaining in place. Immunochemically, it represents PIgM with one type of light chain. The concentration of PIgM in blood serum with Waldenström macroglobulinemia ranges from 30 to 79 g/l. In 55-80% of patients, Bence Jones protein is detected in the urine. The concentration of normal Ig in the blood decreases. Renal failure occurs infrequently.

Lymphomas. IgM-secreting lymphomas are most often recorded, paraproteinemic lymphomas secreting IgG take second place, lymphomas with IgA paraproteinemia are detected extremely rarely. A decrease in the concentration of normal Ig (usually to a small extent) in lymphomas is recorded in most patients.

Heavy chain diseases are B-cell lymphatic tumors accompanied by the production of monoclonal fragments of Ig heavy chains. Heavy chain diseases are observed very rarely. There are 4 types of heavy chain disease: α, γ, μ, δ. γ heavy chain disease usually occurs in men under 40 years of age and is characterized by enlargement of the liver, spleen, lymph nodes, swelling of the soft palate and tongue, erythema, and fever. Bone destruction, as a rule, does not develop. The concentration of pathological globulin in the blood serum is low, ESR is normal. Lymphoid cells and plasma cells of varying degrees of maturity are found in the bone marrow. The disease progresses quickly and ends in death within a few months. Heavy chain disease is detected mainly in older people and is more often manifested by hepatosplenomegaly. The tumor substrate is lymphoid elements of varying degrees of maturity. Isolated cases of δ heavy chain disease have been described; it occurs as myeloma. Heavy chain disease α is the most common form, occurring mainly in children and people under 30 years of age, with 85% of cases reported in the Mediterranean region. Immunoelectrophoresis of blood serum and urine is the only method for diagnosing the disease, since the classic M-gradient in the electropherogram of serum proteins is often absent.

Associated paraproteinemia accompanies a number of diseases in the pathogenesis of which immune mechanisms play a role: autoimmune diseases, tumors, chronic infections. These diseases include AL amyloidosis and cryoglobulinemia.


[13-099 ] Screening for multiple myeloma and paraproteinemias (immunofixation of blood serum with pentavalent serum)

2740 rub.

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This test is designed to detect monoclonal immunoglobulin (paraprotein) using a combination of clinical electrophoresis and immunofixation. As a result of the separation of blood serum proteins by electrophoresis, the paraprotein (also called the M-peak or M-gradient) undergoes migration in the form of a compact band, which makes it noticeable against the background of other protein fractions. The immunofixation method makes it possible to reliably identify the monoclonal immunoglobulin component and determine its absolute content in blood serum.

Synonyms Russian

Electrophoretic separation of serum proteins, clinical electrophoresis and immunofixation, Rustitsky-Kahler disease screening, myeloma screening, myelomatosis screening, reticuloplasmocytosis screening, generalized plasmacytoma screening.

SynonymsEnglish

Serum protein electrophoresis, immunofixation electrophoresis, multiple myelomascreening, plasmacell scancerscreening, plasmacell myeloma screening, monoclonal gammopathy screening.

Research method

Immunofixation.

Units of measurement

G/L (grams per liter).

What biomaterial can be used for research?

Venous blood.

How to properly prepare for research?

  • Do not smoke for 30 minutes before the test.

General information about the study

Diagnosis of multiple myeloma is carried out using a symbiosis of two research methods - clinical electrophoresis and immunofixation - and consists of identifying the presence of a paraprotein in the blood serum for its subsequent typing. Using this study, it is possible to identify not only myeloma, but also other lymphoproliferative diseases, as well as amyloidosis, polyneuropathy, hemolytic anemia, cryoglobulinemia, and kidney damage.

The main symptom of these diseases from the point of view of laboratory diagnosis is an increase in the synthesis of immunoglobulin. The electrophoresis method allows you to separate blood serum proteins and isolate immunoglobulin - as a result of splitting, it stands out against the background of other protein fractions in the form of a migrating band. This immunoglobulin is called a paraprotein (also called monoclonal immunoglobulin, M-peak or M-gradient). It is this tumor marker if the patient has hemato-oncological diseases.

Clinical manifestations of multiple myeloma are associated with bone destruction - these can be pathological fractures, bone pain, anemic syndrome, decreased hemoglobin in the blood, hyperviscosity syndrome, thrombosis and bleeding. Bone destruction leads to an increase in the amount of calcium in the blood, which in turn leads to calcium deposits in the kidneys, lungs and stomach lining. Also, with myeloma, frequent bacterial infections are observed in the patient - this is due to a decrease in the amount of normal immunoglobulins and disturbances in the process of antibody formation.

The presence of multiple myeloma is directly related to the proliferation of plasmacytes capable of secreting paraprotein or its fragments. At the time of diagnosis, the concentration of monoclonal immunoglobulin in the blood serum most often exceeds 25 g/l. Monitoring and monitoring changes in the level of paraprotein concentration allows monitoring the patient’s condition and assessing the effectiveness of myeloma treatment. If the disease is present, control tests to monitor changes in paraproteinan concentrations during therapy should be performed every 3 months.

In myeloma, the paraprotein in the blood serum in 60% of cases is IgG, 20% is IgA. This 20% relates to the definition of Bence Jones myeloma - in this case, it is also necessary to monitor the production of free light chains (kappa or lambda) and their presence in the urine. Quite rarely (in 2–4% of cases) in the presence of myeloma, the presence of a biclonal paraprotein may also be noted.

Lymphoma in which monoclonal IgM is actively produced is called Waldenström macroglobulinemia. In this type of lymphoma, tumor cells are diffusely distributed in the spleen, bone marrow and lymph nodes. Blood viscosity increases and a number of clinical symptoms appear: blindness, confusion, bleeding tendency, hypertension, heart failure - this is associated with an increase in the concentration of monoclonal IgM to 30 g/l or more. In other types of lymphomas, the concentration of IgM paraproteins usually does not exceed 30 g/l, although they are found in 20% of patients.

In addition to the above, monoclonal paraprotein can be detected in some non-tumor diseases. This may be essential cryoglobulinemia, paraproteinemic chronic polyneuropathy, cold hemolytic anemia, AL amyloidosis of the kidneys and internal organs, light chain deposition disease. Also, paraprotein in blood serum is detected in Castleman disease, POEMS syndrome and myxedematous lichen.

If paraproteinemia does not progress to multiple myeloma or another disease within 5 years, we are talking about benign paraproteinemia. In this case, the paraprotein concentration is usually below 3 g/l.

According to statistics, paraproteinemia is most often detected in patients over 50 years of age. In persons over 65 years of age, the detection rate of the disease reaches 4-10%. In most cases, these are asymptomatic monoclonal gammopathies of undetermined significance (MGUS) - this is paraproteinemia without other signs of oncohematological disease. In this case, continuous concentration monitoring is not required.

If paraproteinemia is detected in patients under 50 years of age, it is necessary to conduct follow-up examinations. This is associated with an increased risk of developing multiple myeloma. If a paraprotein concentration is detected above 15 g/l, it is necessary to conduct a number of additional studies: electrophoresis of a 24-hour urine sample and immunofixation every 3-6 months.

What is the research used for?

  • Diagnosis of the cause of clinical symptoms (back pain, spontaneous fractures, frequent bacterial infections, polyneuritis, hemolytic anemia, nephrotic syndrome, skin purpura, elevated ESR syndrome, hypercalcemia, amyloidosis of internal organs, endocrinopathy, organomegaly).
  • Monitoring paraprotein concentration levels in monoclonal gammopathy of unknown significance.
  • Evaluation of the effectiveness of therapy for myeloma and other gammopathies.

What do the results mean?

Reference values: paraprotein (IgG, A, M, kappa/lambda) was not detected.

Paraprotein in blood serum present if the patient has:

  • transient paraproteinemia;
  • monoclonal gammopathy of unknown significance;
  • benign paraproteinemia;
  • paraproteinemic polyneuropathy;
  • cryoglobulinemia;
  • cold hemolytic anemia;
  • AL amyloidosis or light chain deposition disease;
  • lichen mysedema;
  • POEMS syndrome (polyneuropathy with organomegaly);
  • multiple myeloma;
  • Waldenström's macroglobulinemia;
  • lymphoma and CLL (chronic lymphocytic leukemia);
  • heavy chain diseases.

No paraprotein in blood serum allows you to almost completely exclude the possibility of a diagnosis of gammopathy (to confirm, it is necessary to exclude the presence of Bence-Jones protein in the urine).



Important Notes

The interpretation of the study results is not a diagnosis and contains information for the attending physician to use the information along with other sources (anamnesis, medical history, other studies).

Clinical and biochemical blood test - main indicators

Who orders the study?

Oncologist, therapist, hematologist, nephrologist, urologist.

Literature

1. Lapin S.V. Totolyan A.A. Immunological laboratory diagnosis of autoimmune diseases. Publishing house "Man", St. Petersburg - 2010.

2. Tietz Clinical guide to laboratory tests. 4th ed. Ed. Wu A.N.B.- USA, W.B Sounders Company, 2006, 1798 p.

3. Conrad K, Schlosler W., Hiepe F., Fitzler M.J. Autoantibodies in Organ Specific Autoimmune Diseases: A Diagnostic Reference/ PABST, Dresden – 2011.

4. Conrad K, Schlosler W., Hiepe F., Fitzler M.J. Autoantibodies in Systemic Autoimmune Diseases: A Diagnostic Reference/ PABST, Dresden – 2007.

5. Gershvin ME, Meroni PL, Shoenfeld Y. Autoantibodies 2nd ed./ Elsevier Science – 2006.

6. Shoenfeld Y., Cervera R, Gershvin ME Diagnostic Criteria in Autoimmune Diseases / Human Press - 2008.

Service code: 31.4.3.4051
2895 ₽
M-gradient, typing. Serum electrophoresis, immunofixation with a panel of antisera (separately for IgG, IgA, IgM, kappa, lambda), quantitative assessment of M protein

Laboratory diagnostics
: proteins and amino acids.

Indications

  • Paraprotein typing.
  • Differential diagnosis of monoclonal gammopathies.
  • Evaluation of the effectiveness of therapy for myeloma and other gammopathies
Preparation
It is preferable to wait 4 hours after your last meal; there are no mandatory requirements.

Description
Identification and typing of monoclonal immunoglobulins.
Immunoglobulins are proteins that have antibody activity (the ability to specifically bind certain antigens). Unlike most serum proteins, which are produced in the liver, immunoglobulins are produced by plasma cells, descendants of B-lymphocyte precursor stem cells in the bone marrow. Based on structural and functional differences, there are 5 classes of immunoglobulins - IgG, IgA, IgM, IgD, IgE and a number of subclasses. Polyclonal increases in immunoglobulins are a normal response to infections.

Monoclonal gammomapathies are conditions when a clone of plasma cells or B lymphocytes (a population of cells originating from a single precursor B cell) produces an abnormal amount of immunoglobulin. Such conditions may be benign or a manifestation of disease. Monoclonal gammopathies are identified by the appearance of an abnormal protein band on serum or urine electrophoresis.

Immunoglobulin molecules consist of one or more structural units built according to a single principle - two identical heavy chains and two identical light peptide chains - kappa or lambda. Varieties of heavy chains are the basis for dividing immunoglobulins into classes. Immunoglobulin chains have constant and variable regions, the latter being associated with antigen specificity.

Immunoglobulin produced by one clone of cells has an identical structure - it represents one class, subclass, and is characterized by an identical composition of heavy and light chains. Therefore, if an abnormally large amount of monoclonal immunoglobulin is present in the serum, during the electrophoretic separation of serum proteins it migrates in the form of a compact band, which stands out against the background of the standard distribution pattern of serum protein fractions. When describing the results of serum protein electrophoresis, it is also called paraprotein, M-peak, M-component, M-protein or M-gradient. In structure, such a monoclonal immunoglobulin can be a polymer, monomer, or fragment of an immunoglobulin molecule (in the case of fragments, these are often light chains, less often heavy chains). Light chains are able to pass through the kidney filter and can be detected by urine electrophoresis.

Identification of monoclonal paraproteins is based on the use of protein electrophoresis. Sometimes fibrinogen and CRP, which migrate into the gamma fraction, can be mistakenly regarded as paraproteins. The immunoglobulin nature of the identified monoclonal component is confirmed by immunofixation of separated proteins with a specific polyvalent precipitating antiserum directed against immunoglobulins (test no. 4050). When confirming the presence of monoclonal immunoglobulin, densitometry is performed and its quantitative content is determined. For complete identification (typing) of the monoclonal component, a detailed study using electrophoresis and immunofixation with a detailed panel of antisera against IgG, IgA, IgM, kappa and lambda chains is required (test No. 4051). In diagnosis and prognosis, the class of the identified paraprotein, its concentration at the time of diagnosis, and the rate of increase in its concentration over time are taken into account. The presence of paraprotein is a marker of a number of hemato-oncological diseases.

Multiple myeloma is a classic hematological disease caused by malignant proliferation of plasma cells secreting monoclonal immunoglobulin (paraprotein) or its fragments. Plasma cells often proliferate diffusely in the bone marrow, the disease leads to osteolytic lesions of the bones, reduction of other bone marrow cells, which leads to anemia, thrombocytopenia, leukopenia, and inhibits the development of normal clones of plasma cells. Patients may present with localized symptoms of bone pathology (pain, fractures) or nonspecific symptoms (weight loss, anemia, bleeding, recurrent infections, or renal failure). In most patients, at the time of diagnosis, the paraprotein concentration exceeds 25 g/l. In myeloma, the paraprotein in the blood serum is most often represented by IgG (60%), less often IgA (20%) and about 20% are Bence-Jones myeloma associated with the production of free kappa or lambda light chains (20%), which can be found in urine. Sometimes in myeloma, a biclonal paraprotein may be observed, represented by immunoglobulins of different classes or of the same class, but containing light chains of different classes. IgD and IgE myeloma are rare. Determination of paraprotein concentration is used to monitor the effectiveness of treatment for myeloma; such monitoring for myeloma during therapy should be carried out every 3 months. If the paraprotein content has decreased below the detectable level, it is advisable to repeat the measurement after 6 or 12 months.

Waldenström's macroglobulinemia is a lymphoma with overproduction of monoclonal IgM. Lymphoplasmacytic tumor cells with a characteristic immunophenotype are diffusely distributed in the lymph nodes, spleen and bone marrow. High concentrations of monoclonal IgM often exceed 30 g/L and lead to increased blood viscosity and a range of clinical manifestations including confusion, blindness, bleeding tendency, heart failure and hypertension. With macroglobulinemia, paraproteinemic polyneuropathy, cold hemolytic anemia and cryoglobulins are often observed. In other types of lymphomas and chronic lymphocytic leukemia, paraproteins of the IgM class are observed in 20% of patients, but the concentration of paraprotein is usually lower than 30 g/l.

Heavy chain disease (Franklin disease) is accompanied by the synthesis of only the IgG-gamma heavy chain, without the accompanying light chain. This extremely rare disease is characterized by swelling of the soft palate and lymphoid infiltration. Also rarely observed is alpha heavy chain disease, which causes chronic diarrhea and malabsorption caused by lymphoid infiltration of the intestinal wall.

Monoclonal paraprotein can be detected in a number of non-tumor diseases, in particular, with essential cryoglobulinemia (usually IgM), paraproteinemic chronic polyneuropathy, cold hemolytic anemia, AL amyloidosis of the kidneys (free lambda chains), and internal organs, light chain deposition disease. Serum paraprotein is also observed in Castleman disease (IgM/lambda), POEMS syndrome (polyneuropathy with organ megalia) and lichen myxedema (IgG/kappa).

During screening examinations, the frequency of detection of paraproteinemia increases sharply in the population after reaching 50 years of age and reaches 4–10% in people over 65 years of age. However, the majority of newly diagnosed paraproteinemias in the general population are asymptomatic monoclonal gammopathies of undetermined significance (MGUS). The paraprotein concentration in MGUS is significantly lower than 30 g/l and usually does not exceed 10–15 g/l. In addition, in MGUS, the paraprotein is detected against the background of polyclonal immunoglobulins, i.e., inhibition of the normal synthesis of other immunoglobulins does not occur. The term “MGUS” indicates cases of paraproteinemia without other signs of oncohematological disease, which require annual monitoring in order not to miss the moment of malignancy of the process. When paraproteins are detected in patients under 50 years of age, even more frequent repeat examinations are necessary, since they have a high risk of developing multiple myeloma. If the M-protein concentration is more than 15 g/l, regardless of age, extensive testing is recommended, including electrophoresis of a 24-hour urine sample and immunofixation every 3-6 months, since the risk of malignant transformation is very high. Benign paraproteinemia is distinguished, which is characterized by the persistence of paraprotein without progression to multiple myeloma or another disease over 5 years of observation. With transient paraproteinemia, the paraprotein concentration is usually below 3 g/l.

Determination of quantitative and qualitative changes in the main fractions of blood protein, used for diagnosis and control of treatment of acute and chronic inflammation of infectious and non-infectious origin, as well as oncological (monoclonal gammopathies) and some other diseases.

With the proliferation of a clone of plasma cells, the synthesis of immunoglobulin increases, represented by one class, subclass and isotype, which includes heavy and light protein chains of the same type. During the electrophoretic separation of blood serum proteins, this immunoglobulin migrates in the form of a compact band, which is determined against the background of other protein fractions. This immunoglobulin is called monoclonal immunoglobulin or paraprotein. When electrophoresing serum proteins, it is called the M-gradient. Paraprotein is a tumor marker for a number of hemato-oncological diseases.

Multiple myeloma is a classic hematological disease that is caused by the proliferation of plasma cells secreting monoclonal immunoglobulin (paraprotein) or its fragments. In most cases, at the time of diagnosis, the paraprotein concentration exceeds 25 g/l.

In myeloma, the paraprotein in the blood serum is most often represented by IgG (60%), less often IgA (20%). The remaining approximately 20% of cases are Bence Jones myeloma, associated with the production of free kappa or lambda light chains (20%). In 2–4% of myeloma cases, a biclonal paraprotein may be observed, represented by immunoglobulins of different classes or of the same class, but containing light chains of different classes. Changes in paraprotein concentration serve as an indicator of the effectiveness of myeloma treatment. Monitoring of PP concentrations in myeloma during therapy should be carried out every 3 months. If the PP content has decreased below the detectable level, it is advisable to repeat the measurement after 6 or 12 months.

Waldenström's macroglobulinemia is a lymphoma with overproduction of monoclonal IgM. Lymphoplasmacytic tumor cells with a characteristic immunophenotype are diffusely distributed in the lymph nodes, spleen and bone marrow. High concentrations of monoclonal IgM often exceed 30 g/L and lead to increased blood viscosity and a range of clinical manifestations including confusion, blindness, bleeding tendency, heart failure and hypertension. With macroglobulinemia, paraproteinemic polyneuropathy, cold hemolytic anemia and cryoglobulins are often observed. In other types of lymphomas and chronic lymphocytic leukemia, paraproteins of the IgM class are observed in 20% of patients, but the concentration of paraprotein is usually lower than 30 g/l.

Heavy chain disease (Franklin disease) is accompanied by the synthesis of only the IgG-gamma heavy chain, without the accompanying light chain. This extremely rare disease is characterized by swelling of the soft palate and lymphoid infiltration. Also rarely observed is alpha heavy chain disease, which causes chronic diarrhea and malabsorption caused by lymphoid infiltration of the intestinal wall.

During screening examinations, the frequency of detection of paraproteinemia increases sharply in the population after reaching 50 years of age and reaches 4–10% in people over 65 years of age. However, the majority of newly diagnosed paraproteinemias in the general population are asymptomatic monoclonal gammopathies of undetermined significance (MGUS). The paraprotein concentration in MGUS is significantly lower than 30 g/l and usually does not exceed 10–15 g/l. In addition, in MGUS, the paraprotein is detected against the background of polyclonal immunoglobulins, i.e., inhibition of the normal synthesis of other immunoglobulins does not occur. The term “MGUS” indicates cases of paraproteinemia without other signs of oncohematological disease, which require annual monitoring in order not to miss the moment of malignancy of the process. When paraproteins are detected in patients under 50 years of age, even more frequent repeat examinations are necessary, since they have a high risk of developing multiple myeloma. If the M-protein concentration is more than 15 g/l, regardless of age, extensive testing is recommended, including electrophoresis of a 24-hour urine sample and immunofixation every 3-6 months, since the risk of malignant transformation is very high. Benign paraproteinemia is distinguished, which is characterized by the persistence of paraprotein without progression to multiple myeloma or another disease over 5 years of observation. With transient paraproteinemia, the paraprotein concentration is usually below 3 g/l.

Indications for prescribing the study:

1. Paraprotein typing.

2. Differential diagnosis of monoclonal gammopathies.

3. Assessing the effectiveness of therapy for myeloma and other gammopathies.

Interpretation of results:

Positively:

  • Monoclonal gammopathies of unknown significance, benign paraproteinemias;
  • Multiple myeloma;
  • Waldenström's macroglobulinemia;
  • Lymphoma and chronic lymphocytic leukemia;
  • Heavy chain disease;
  • Paraproteinemic polyneuropathy;
  • AL amyloidosis or light chain deposition disease;

Negative:

  • Normally, the M gradient is not detected in serum.