Immunofixation of Bence Jones protein with a panel of antisera

Description

Synonyms (rus): Bence-Jones protein, free light chains in urine
Synonyms (eng): Bence-Jones protein, free light chains kappa nad lambda in urine

Biomaterial: Single urine

Indicator(s): Bence-Jones protein

Method(s): Agarose gel electrophoresis, Immunofixation

Container type and preanalytical features: Urine preservative tube, 8 ml

Free monoclonal light chains of immunoglobulins in the urine are called Bence Jones protein. Bence Jones proteinuria is a variant of prerenal proteinuria, which is caused by excess protein in the blood plasma. Detection of a paraprotein in urine (Bence Jones protein) during a screening test of a urine sample using immunofixation indicates a monoclonal gammopathy. The most likely presence is those forms of gammopathies that are accompanied by the secretion of free light chains of immunoglobulins (light chain disease, other forms of myeloma, MGUS with paraprotein in the urine, etc.). At the same time, light chains have a nephrotoxic effect, so over time, depending on the level of damage to the nephron, glomerular or tubular proteinuria may occur. In rare cases, paraprotein in urine may be represented not by free light chains, but by intact paraprotein (whole molecules of monoclonal immunogloblin), i.e. is not a Bence Jones protein by definition.

BENCE JONES PROTEIN

BENCE JONES WHITE

K (H. Bence-Jones, 1813-1873, English physician; synonym:
Bence-Jones protein body, Bence-Jones albumin
) is a urine protein that appears in it under certain pathological conditions. It has the property of precipitating when heated to a temperature of 50-60°, dissolving when heated to temperatures close to the boiling point of the solution, and precipitating again when cooled. By these properties, proteinuria with the presence of Bence-Jones proteins in the urine (Bence-Jones proteinuria) can be distinguished from other types of proteinuria (see), since otherwise it gives all the characteristic reactions to proteins. First described in 1848 by Bence-Jones. The appearance of protein in Bence-Jones's urine is a characteristic symptom of multiple myeloma (see). Bence Jones proteins are light chains of immunoglobulins (see) produced by myeloma cells; molecular weight is about 22 thousand (dimers - in the range of 40-44 thousand). In each individual case of myeloma, meloma proteins and, accordingly, light chains are monoclonal antibodies, that is, homogeneous proteins synthesized by one clone of plasma cells. On the other hand, different patients may have many different Bence Jones proteins belonging to the class of immunoglobulin light chains. Accordingly, the amino acid composition and dietary amino acids of Bence Jones protein isolated from the urine of patients with multiple myeloma are not always the same. Characteristic of Bence Jones protein is the absence or very low content of methionine, histidine, hydroxyproline and high tyrosine content. Bence Jones protein crystallizes easily; Cases of its spontaneous crystallization in urinary tubules and tumors (protein crystals) have been described.

To detect Bence Jones protein in urine, the urine is acidified to a pH of about 5.5, filtered, and heated. Characteristic is the precipitation of the protein at a temperature of about 56°, an increase in the sediment upon further heating to complete dissolution at boiling (Bence-Jones test). To quantify Bence-Jones protein, urine is heated to t° 70°, the protein precipitate is separated by centrifugation, washed with water, alcohol, ether and weighed.

Bence Jones protein is found in the urine of 30-80% of patients with multiple myeloma. The appearance of this protein in the urine has also been described in some cases of leukemia, lymphosarcoma, osteomalacia and a number of other diseases, but currently the appearance of Bence-Jones protein in the urine is considered as an important specific diagnostic symptom of multiple myeloma, also allowing the possibility of its appearance in the urine only in rare cases. cases of extensive bone marrow lesions (eg, myeloid leukemia). The Bence Jones protein content in urine can range from a fraction of a percent to 6-7%; Cases of patients with multiple myeloma excreting up to 50 g of this protein per day have been described. Bence Jones proteinuria is usually accompanied by hyperproteinemia, which is attributed to the presence of myeloma proteins in the blood plasma. Bence Jones protein appears to be produced by myeloma cells.

Bibliography:

Bence-Jones protein and blood proteins in multiple myeloma, in the book: Sovrem. problem onkol., trans. with in., ed. A. II. Serebrova, V. 3(30), ser. B, p. 82, M.. 1952; Gulevich V.S. A rare case of finding protein crystals in ovules, Zhurn. let's experiment biol, i med., vol. 5. D1 15, p. 215, 1927, bibliogr.; Basch N. An introduction to the biochemistry of the cancer cell, p. 269, NY— L., : >62; L ichtwitz L. Klinische Chemie "8. 145, V., 1930; Polonovskl M. et D e 1 b a g e F. Les pro t6 Ines de Bence-Jones, in the book: Ekhrovev annuels biochim. möd., sous la dir. de M. Polonovskl ea, J. 257, P., 1951; Putnam FW Aberra-ona of protein metabolism in multiple myeloma. Physiol. Rev., v. 37, p. 512, 1057.

N. B. Zversky.

Interpretation

The absence of paraprotein (M-gradient) in the urine most likely excludes the diagnosis of paraproteinemia, accompanied by the synthesis of a free light chain, but does not exclude the presence of paraprotein in the blood serum. Detection of a paraprotein in urine (Bence Jones protein), using polyclonal antiserum, during a screening test of a urine sample indicates a hematological malignancy. Urinary paraprotein typing using immunofixation with a panel of antisera may be recommended.

Proteinuria in adults: diagnostic approach

Analysis of urine:

10.04.2009

M. F. Carroll, M.D. and J. L. Temte, M.D., Ph.D.

University of Wisconsin-Madison Medical School, Madison, Wisconsin

Am Fam Physician 2000; 62:1333–40

Translation Ph.D. Kurilyak O.A.

According to population studies, when analyzing urine with diagnostic strips, proteinuria is detected in 17% of patients [1]. However, severe pathology of the urinary tract is confirmed in only no more than 2% of patients in whose urine protein is detected by diagnostic strips [2]. The cause of the development of proteinuria is a number of diseases that can end in either a successful or fatal outcome. The diagnosis of proteinuria must be approached very responsibly, since the diagnosis affects the psychological state of the patient, his career and insurance conditions.

Definition of proteinuria

24 centuries ago, Hippocrates pointed out the connection between “bubbles on the surface of the urine” and kidney disease [3,4]. Nowadays, proteinuria is understood as the excretion of protein in the urine in an amount of more than 150 mg/day. The protein content in the urine of healthy individuals varies significantly and, under certain circumstances, increases to a level that corresponds to proteinuria. In most cases, when urine test strips (eg, Albustix, Multistix) give a positive reaction for protein, we are talking about benign proteinuria, which is not associated with increased morbidity or mortality (Table 1).

Table 1. Common causes of benign proteinuria

Approximately 20% of the total amount of protein that is excreted by the kidneys under physiological conditions is low molecular weight proteins such as immunoglobulins (molecular weight about 20,000 daltons), 40% is represented by high molecular weight albumin (about 65,000 daltons) and 40% are Tamm-mucoproteins. Horsfall, secreted by the distal tubules.

Mechanisms of proteinuria development

Under physiological conditions, barriers to filterable proteins are found in the glomeruli, which consist of specific capillaries that are permeable to fluid and low molecular weight solutes, but effectively prevent the filtration of plasma proteins. The adjacent basement membrane and epithelial cells (podocytes) are coated with negatively charged heparan sulfate proteoglycans [5].

The amount of proteins filtered into the tubular fluid is inversely proportional to the molecular weight and the magnitude of the negative charge of the molecules. Proteins with a molecular weight of less than 20,000 daltons easily pass through the wall of glomerular capillaries [6]. In contrast, under physiological conditions the filtration of albumin, which has a molecular weight of 65,000 daltons and a negative charge, is limited. Proteins with lower molecular weights are reabsorbed mainly in the proximal tubules and only small amounts are excreted in the urine.

There are three pathophysiological mechanisms for the development of proteinuria: glomerular, tubular and prerenal (overflow proteinuria, which occurs when there is excess protein in the plasma) (Table 2) [7].

Table 2. Classification of proteinuria

The most common cause of pathological proteinuria is damage to the glomeruli [8]. With pathology of the glomerular apparatus, the permeability of the glomerular basement membrane increases, which leads to the loss of immunoglobulins and albumin in the urine [7]. Dysfunction of the glomeruli is accompanied by the release of large amounts of protein. Excretion of protein in the urine in amounts exceeding 2 g/day is usually a sign of kidney disease, which occurs with damage to the glomerular apparatus (Table 3) [9].

Table 3. Classification of the causes of proteinuria, taking into account the amount of protein excreted in the urine

Tubular proteinuria occurs in tubulointerstitial pathology, when the reabsorption of low molecular weight proteins (which form part of the physiological glomerular ultrafiltrate) is impaired in the proximal tubules. In tubular diseases, protein is usually excreted in the urine in amounts less than 2 g/day. Pathology of the tubules includes nephrosclerosis in hypertension, as well as tubulointerstitial nephropathy, which is mediated by the use of non-steroidal anti-inflammatory drugs.

In patients with prerenal proteinuria, accompanied by high concentrations of low molecular weight proteins in the plasma, the ability of the proximal tubules to reabsorb filtered proteins is suppressed. In most cases, the cause of hyperproteinemia is excessive production of monoclonal protein in multiple myeloma. Light chains of immunoglobulins (Bence Jones proteins) form a monoclonal peak during electrophoresis of urinary proteins [10]. In table 4 [11] presents a classification of proteinuria, which takes into account the pathophysiological mechanisms of proteinuria development.

Table 4. Classification of the main causes of proteinuria, taking into account the mechanisms of development of this pathology

Diagnosis and quantification of proteinuria

Most clinics and outpatient clinics use diagnostic strips for semi-quantitative determination of protein in urine. If the urine does not contain protein, the test zone of the strip remains yellow. Soluble urine proteins react with dye and buffers, causing the test area to turn green. When testing alkaline urine (pH >7.5), false positive results are obtained in the following cases: when the strip is immersed in the test urine for a long time; when analyzing concentrated urine; with macrohematuria; if there is penicillin, sulfonamides or tolbutamide in the urine; when urine is contaminated with pus, semen or vaginal discharge. False-negative results are obtained when analyzing dilute urine (relative density less than 1.015) and in cases where the urine proteins do not contain albumin, or when the urine proteins have a small molecular weight.

If the level of protein in the urine is below 100 mg/l, the reaction is considered negative. If “traces” of protein are detected in the urine, the protein concentration varies from 100 to 200 mg/l. The results are then expressed in crosses from 1+ to 4+, in particular 1+ (300 mg/l), 2+ (1,000 mg/l), 3+ (3,000 mg/l), 4+ (10,000 mg/l l). This reaction is more sensitive to albumin and to a lesser extent to globulins or globulin fragments (heavy or light chains of immunoglobulins, as well as Bence Jones proteins) [12].

Diagnostic strips and qualitative methods using sulfosalicylic acid can only approximately determine the concentration of protein in the urine; results depend on the amount of urine excreted. Therefore, a weak correlation has been identified between the results obtained by this method and precise quantitative methods [6].

In most patients with persistent proteinuria, the amount of protein in daily urine is determined. In the morning the patient empties the bladder; This urine sample is not used for analysis. Then all urine portions are collected, including the first portion of urine that is excreted the next morning (after sleep). The collected urine is tested for protein as well as creatinine to assess whether the sample was collected correctly. The amount of creatinine released depends on muscle mass, and the concentration of this substance remains constant throughout the day. In young men and middle-aged patients, creatinine is released in amounts from 16 to 26 mg/kg/day, in women this value is 12–24 mg/kg/day. In malnourished patients and the elderly, less creatinine is released.

Along with the study of 24-hour urine, the protein/creatinine ratio is sometimes determined in a randomly collected urine sample; the patient is on the usual regime [13,14]. A correlation between the protein/creatinine ratio and the amount of protein in 24-hour urine has been established in several diseases, including diabetes mellitus, preeclampsia and rheumatic diseases [15–17]. The protein/creatinine ratio is a more accurate laboratory indicator than the amount of protein in daily urine [18]. Fortunately, the protein/creatinine ratio roughly corresponds to the number of grams of protein excreted in urine per day. Thus, a ratio of less than 0.2 corresponds to 0.2 g of protein/day and is considered normal; a ratio of 3.5 corresponds to 3.5 g of protein/day and is considered a sign of proteinuria, the degree of which corresponds to proteinuria in patients with nephrotic syndrome (proteinuria severe).

Diagnostic evaluation of proteinuria

Microscopy of urinary sediment

If proteinuria is found when examining urine with diagnostic strips, microscopy of the urinary sediment is performed (Fig. 1). In table Table 5 lists the elements of organized sediment that are found in certain diseases of the urinary organs [6]. Dysmorphic red blood cells, which appear due to osmotic disturbances in the nephron, are a sign of damage to the glomeruli. With macrohematuria, in contrast to microhematuria, diagnostic strips give a positive reaction to protein.

Signs of infection, which are found by microscopy of urinary sediment, serve as the basis for antibiotic therapy and subsequent urine analysis using diagnostic strips. If changes in urine characteristic of underlying kidney disease are detected, the patient is referred to a nephrologist.

Transient proteinuria

If questionable results are obtained during microscopy of urinary sediment, and the protein content in the urine varies from “traces” to 2+, the analysis of morning urine is repeated at least twice within a month. For this purpose, diagnostic strips are used. If the degree of proteinuria is 3+ or 4+, a quantitative method is used to determine the protein excreted in the urine. If protein is not found during repeated urine tests with diagnostic strips, it is possible that the patient’s proteinuria is transient. This condition is not associated with increased morbidity or mortality, so follow-up is not necessary.

Table 5. Interpretation of urinary sediment microscopy results

Persistent proteinuria

If a diagnosis of persistent proteinuria is made, a detailed history is obtained and a physical examination is performed to exclude systemic diseases in which the kidneys are involved in the pathological process (Table 4) [11]. Find out whether the patient took medications.

A randomly collected urine sample is used to determine the protein/creatinine ratio. If a patient with an established diagnosis (eg, diabetes mellitus or decompensated heart failure) has a creatinine clearance within the normal range, treat the underlying disease and carefully monitor proteinuria and renal function (glomerular filtration). A patient with moderate or severe proteinuria and reduced glomerular filtration rate, or an unclear cause for the development of proteinuria, after consultation with a nephrologist, additional studies are prescribed. In table Table 6 lists the main studies that are performed on a patient with severe proteinuria [19].

Note: creatinine clearance is calculated using the Cockcroft‑Gault formula:

(140 – age) x body weight (kg)

Creatinine clearance = ––––––––––––––––––––––––––––––––––––––––––

Serum creatinine (mg/dL) x 72

When studying creatinine clearance in women, the result obtained is multiplied by 0.85. In cases of severe ascites or obesity, ideal body weight is used for calculation [6].

Nephrotic syndrome

Nephrotic syndrome and proteinuria, the degree of which corresponds to that of nephrotic syndrome, are signs of pathology of the glomerular apparatus of the kidneys. Diagnostic criteria for nephrotic syndrome: severe proteinuria or proteinuria, the degree of which corresponds to that of nephrotic syndrome, hypoalbuminemia, edema, hyperlipidemia and lipiduria. The pathological process is represented by primary or secondary glomerulonephropathy, as indicated in Table. 4 [11]. Common secondary causes are diabetic nephropathy, amyloidosis, and systemic lupus erythematosus.

Table 6. Diagnostic tests for proteinuria

Orthostatic proteinuria

In patients under 30 years of age with proteinuria less than 2 g/day and normal creatinine clearance, orthostatic, or postural, proteinuria is excluded. This benign condition occurs in 3–5% of individuals during adolescence and young adulthood. In these patients, when standing, protein is excreted in increased amounts, but when lying down, the amount of protein in the urine remains within normal limits. In order to diagnose orthostatic proteinuria, a comparative analysis of both samples is performed. In the morning the patient empties the bladder; this urine sample is not examined. Urine is collected during the day, for 16 hours, while the patient is on his usual regimen. They finish collecting urine in the evening, before going to bed. A second urine sample, 8 hours in advance, is collected in the morning.

In typical cases, in the first urine sample the protein content is increased, while in the morning urine collected after sleep, the protein concentration does not differ from the norm. In patients with pathology of the glomerular apparatus of the kidneys, protein excretion is reduced in the standing position, but does not normalize (less than 50 mg per 8 hours) in the supine position, as is observed with orthostatic proteinuria.

Orthostatic proteinuria is a benign condition. According to dynamic observations, renal function remains within normal limits for 20–50 years [20,21]. In these patients, blood pressure is measured annually and a general clinical urine test is performed.

Isolated proteinuria

The diagnosis of isolated proteinuria is established if a patient with an increased concentration of protein in the urine has blood pressure within the normal range, there are no signs of systemic disease, renal function is not impaired, and no pathology is found on microscopic examination of urinary sediment. Typically, protein is excreted in amounts less than 2 g/day. The risk of developing kidney failure in these patients after 10 years is 20%. Therefore, in these patients, blood pressure is measured every 6 months, urine is examined, and creatinine clearance is determined [7]. Isolated proteinuria, in which protein is excreted in amounts greater than 2 g/day, is rare and is usually a sign of glomerulonephritis [7]. These patients are prescribed additional studies, as well as a consultation with a nephrologist.

Conclusion

The clinical significance of proteinuria varies widely. A systematic approach to a patient who has increased protein content in the urine allows the clinician to differentiate between benign and pathological processes that are the cause of the development of proteinuria. A diagnostic algorithm, including determination of the protein/creatinine ratio, helps to establish an accurate and objective diagnosis. Patients with an unknown cause for the development of proteinuria after a diagnostic study are referred to a nephrologist. In addition, proteinuria more than 2 g/day is a likely sign of glomerular pathology; such patients require consultation with a nephrologist.

Literature

1. Pegg JF, Reinhardt RW, O'Brien JM. Proteinuria in adolescent sports physical examinations. J Fam Pract 1986;22:80-1.
2. Woolhandler S, Pels RJ, Bor DH, Himmelstein DU, Lawrence RS. Dipstick urinalysis screening of asymptomatic adults for urinary tract disorders: I. hematuria and proteinuria. JAMA 1989;262:1214-9.
3. Beetham R, Cattell WR. Proteinuria: pathophysiology, significance and recommendation for measurement in clinical practice. Ann Clin Biochem 1993;30(pt 5):425-34.
4. Adams F. The genuine works of Hippocrates. Vol 2. London: Sydenham Society, 1849:766.
5. Kanwar YS. Biophysiology of glomerular filtration and proteinuria. Lab Invest 1984;51:7-21.
6. Larson TS. Evaluation of proteinuria. Mayo Clin Proc 1994;69:1154-8.
7. Abuelo JG. Proteinuria: diagnostic principles and procedures. Ann Intern Med 1983;98:186-91.
8. Stone R.A. Office evaluation of the patient with proteinuria. Postgrad Med 1989;86(5):241-4.
9. McConnell KR, Bia MJ. The evaluation of proteinuria: an approach for the internist. Res Staff Physician January 1994:41-8.
10. Longo DL. Plasma cell disorders. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of internal medicine. 14th ed. New York: McGraw-Hill, 1998:712-8.
11. Glassrock R.J. Proteinuria. In: Massry SJ, Glassrock RJ, eds. Textbook of nephrology. 3d ed. Baltimore: Williams & Wilkins, 1995:602.
12. Laffeyette RA, Perrone RD, Levey AS. Laboratory evaluation of renal function. In: Schrier RW, Gottschalk CW, eds. Diseases of the kidney. Boston, Mass: Little Brown, 1996:339.
13. Ginsberg JM, Chang BS, Matarese RA, Garella S. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med 1983;309:1543-6.
14. Schwab SJ, Christensen RL, Dougherty K, Klahr S. ​​Quantitation of proteinuria by the use of protein-to-creatinine ratios in single urine samples. Arch Intern Med 1987;147:943-4.
15. Rodby RA, Rohde RD, Sharon Z, Pohl MA, Bain RP, Lewis EJ. The urine protein to creatinine ratio as a predictor of 24-hour protein excretion in type 1 diabetic patients with nephropathy: the Collaborative Study Group. Am J Kidney Dis 1995;26:904-9.
16. Saudan PJ, Brown MA, Farrell T, Shaw L. Improved methods of assessing proteinuria in hypertensive pregnancy. Br J Obstet Gynaecol 1997;104:1159-64.
17. Ralston SH, Caine N, Richards I, O'Reilly D, Sturrock RD, Capell HA. Screening for proteinuria in a rheumatology clinic: comparison of dipstick testing, 24-hour urine quantitative protein, and protein/creatinine ratios in random urine samples. Ann Rheum Dis 1988;47:759-63.
18. Ruggenenti P, Gaspari F, Perna A, Remuzzi G. Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24-hour urine protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic renal disease in patients without diabetes . BMJ 1998;316:504-9.
19. Krause ES. Proteinuria. In: Barker LR, Burton JR, Zieve PD, eds. Principles of ambulatory medicine. 5th ed. Baltimore: Williams & Wilkins, 1999:546.
20. Springberg PD, Garrett LE Jr, Thompson AL Jr, Collins NF, Lordon RE, Robinson RR. Fixed and reproducible orthostatic proteinuria: results of a 20-year follow-up study. Ann Intern Med 1982;97:516-9.
21. Rytand DA, Spreiter S. Prognosis in postural (orthostatic) proteinuria: forty to fifty-year follow-up of six patients after diagnosis by Thomas Addis. N Engl J Med 1981;305:618-21.

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general characteristics

Proteins excreted in the urine represent a small part of the proteins filtered in the renal glomeruli. The main part (98%) is absorbed back (reabsorbed) in the proximal tubules of the kidneys. The main excretion of protein usually occurs during the daytime (walking and upright body position increase the effect of hemodynamic forces on glomerular filtration). Functional proteinuria (a state of increased protein loss in the urine in a patient with healthy kidneys) can be observed with hemodynamic stress caused by high fever, congestive heart failure, cooling, or any acute diseases of the internal organs. This proteinuria disappears after the cause that caused it is eliminated. Impaired ability of the glomerular filter to selectively retain negatively charged proteins leads to selective proteinuria - the loss of low-molecular charged proteins (albumin, etc.). Loss of large amounts of urinary protein (>3 g/day) is almost always associated with disruption of the glomerular filter function regarding protein charge or size, leading to nephrotic syndrome. In some pathological conditions, protein loss is observed due to impaired protein reabsorption in the proximal tubule (certain kidney diseases, side effects of certain drugs and toxic substances, immune processes, infections, systemic diseases). By origin, proteinuria can be prerenal, renal and postrenal. Prerenal proteinuria is caused by an increase in the concentration of plasma proteins during tissue breakdown and paraproteinemia, renal – by kidney pathology, postrenal – by pathology of the urinary tract.

Urine collection instructions

The nurse will give you the necessary supplies:

• plastic container for collecting urine; manual urinal (issued to men);
• a cup for collecting urine (issued to women);
• if you are receiving hospital treatment, you may be given a bedpan;

Immediately before the start of daily urine collection

You must begin counting the urine collection period with an empty bladder. Immediately before the start of the daily collection, urinate in the toilet and flush. Then write down the date and time. This moment will be the beginning of the urine collection period. The collection will end in 24 hours.

Collection start date: ___________________ Collection start time: _________________

During the 24-hour urine collection period

• Collect all urine. Urinate only into a urine bag, urine collection cup, or bedpan. To use a urine collection cup, place it under the toilet seat and urinate into it.
• If you are in hospital, seek help if necessary.

After daily urine collection

If you collected urine at home:

• within 24 hours after the end of urine collection, you will be given an appointment with a doctor; Bring a container of urine to this appointment;
• If you forget to collect any urine during the collection period, tell your nurse;

If you collected urine while in the hospital:

• A nurse or nursing assistant will take the container of urine from you.
• If you forget to collect any urine during the collection period, tell your nurse or nursing assistant.

to come back to the beginning

What to do if a protein is detected

As already mentioned, Bence Jones protein is a tumor marker for myeloma. However, it is impossible to make an accurate diagnosis from just one urine test. Therefore, the doctor prescribes additional tests:

1. Clinical studies of blood and urine. Patients with multiple myeloma usually have elevated ESR and decreased white blood cells. Pathological casts and red blood cells are detected in urine.
2. Urine examination using the Zimnitsky method. Allows you to identify signs of renal failure, which often develops with pathologies of the hematopoietic system.
3. Biochemical blood test. In patients with bone marrow diseases, the metabolism of minerals and proteins is impaired, which is reflected in the results of the study.
4. Bone marrow puncture. This study makes it possible to detect malignant changes in cells with great accuracy.
5. X-ray of the skull, spine and ribs. With myeloma, the image shows a significant decrease in bone density, and sometimes signs of fractures.

Bone marrow diseases require persistent and long-term treatment. Patients are prescribed a course of antitumor chemotherapy drugs, radiation therapy and blood transfusions. In severe cases, a bone marrow transplant is performed.

At the same time, therapy is carried out for developing renal failure. Patients are advised to follow a diet with limited protein in food.

It is important to remember that the earlier treatment for myeloma is started, the more favorable the prognosis of the disease. At an early stage, it is still possible to avoid the proliferation of malignant cells. In advanced cases, the survival rate of patients decreases sharply. Testing urine for Bence-Jones protein allows one to identify dangerous diseases at an early stage, begin treatment on time, and thereby save the patient’s life.

Detailed description of the study

Screening for M-gradient (Bence-Jones protein, M-gradient) in 24-hour urine is one of the methods for diagnosing paraproteinemic hemoblastoses. The latter form a large group of diseases for which a common feature is the synthesis of an inadequate amount of paraproteins - pathological immunoglobulins. These diseases are also called immunoglobulin-secreting lymphomas.

Normal immunoglobulins, or antibodies, are protein molecules that serve to protect against microorganisms and foreign substances. Antibodies contain two light and two heavy polypeptide chains that are interconnected. Heavy chains can be of five different types, designated by the symbols: γ, α, μ, δ, ε. They correspond to 5 classes of Ig - G, A, M, D, E. Bence Jones protein is light polypeptide chains of immunoglobulins, which have several types: κ (kappa) and λ (lambda).

As noted earlier, paraproteinemic hemoblastoses represent a whole group of diseases, which include:

1. Multiple myeloma (MM);
2. Solitary plasmacytomas;
3. Waldenström's macroglobulinemia (MW);
4. Lymphomas with monoclonal secretion of lg;
5. Ig heavy chain diseases (IHC);
6. Difficult to classify Ig-secreting tumors.

The named pathologies differ from each other not only in the nature of their course and clinical picture, but also in the immunochemical (specific) properties of pathological immunoglobulins. The most common paraproteinemic hemoblastosis is multiple myeloma (MM), which is also called plasma cell myeloma, multiple myeloma. This pathology is associated with a pathological increase in the number of so-called myeloma cells and their production of paraproteins.

The causes of the disease in humans are not fully known, but it is believed that the decisive role in the development of plasma cell myeloma belongs to chronic stimulation of the immune system after infection with viruses, bacteria or after exposure to radiation and other factors harmful to the human body. The disease may not manifest itself clinically for a relatively long time: from several months to 2-3 years or more.

The symptoms of plasma cell myeloma are varied, but they are largely determined by the infiltration of the bone marrow by plasma cells and damage to internal organs. Clinically, MM manifests itself with symptoms that are caused by bone damage. These include:

1. Bone pain;
2. Pathological fractures;
3. Compression of the spinal cord by vertebrae during fractures;
4. Pain caused by damage to the nerve roots of the spinal cord.

Multiple myeloma can also manifest itself as:

1. Increased urination;
2. Disorders of the gastrointestinal tract (nausea and vomiting);
3. Asthenic syndrome - weakness and malaise;
4. Edema;
5. Anemia;
6. Bleeding;
7. Raynaud's syndrome.

M-gradient screening is carried out using immunofixation, which is a method of selective staining of proteins separated by electrophoresis using antibodies to paraproteins. This technology makes it possible to detect the presence of pathological immunoglobulin light chains in urine and quantify them.

Urine testing can reveal abnormal protein production because in 20% of plasma cell myeloma cases, the tumor produces exclusively immunoglobulin light chains. They have a low molecular weight and are quickly filtered by the kidneys, which may make them undetectable in the blood.

References

1. Multiple myeloma. Clinical recommendations. Association of Oncologists of Russia. National Society of Hematology, 2021. - 222 p.
2. Stryuk, R.I., Maev, I.V. Internal diseases: textbook, 2008. - 496 p.
3. Andreeva, N.E., Balakireva, T.V. Paraproteinemic hemoblastoses. Guide to Hematology / ed. A.I. Vorobyov. 3rd ed. - M., 2003. - T. 2
4. Guyton, A.K., Hall, J.E. Medical physiology / ed. IN AND. Kobrina. - M.: Logosfera, 2008. - 1296 p.
5. Kishkun, A.A. Guide to laboratory diagnostic methods. - M.: GEOTAR-Media, 2007. - 800 p.