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Bence-Jones protein
Last reviewed: 07.07.2025

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The urine of a healthy person does not contain Bence-Jones protein, which is represented by light chains of immunoglobulins that are detected as a result of the formation of malignant tumor processes.
Laboratory tests for the presence of specific low molecular weight proteins are necessary for diagnosing a number of pathological conditions (most often problems with the β-immune system), as well as for determining the effectiveness of the therapy used.
In excess, Bence-Jones protein is produced by plasma cells, moves with the bloodstream, and is excreted through urination. It is the latter property of protein bodies that allows one to suspect the following diseases when examining urine:
- myeloma;
- osteosarcoma;
- plasmacytoma;
- chronic lymphocytic leukemia;
- lymphogranulomatosis;
- primary amyloidosis;
- macroglobulinemia;
- idiapathic monoclonal gammopathy.
The connection between the release of a specific protein and subsequent renal dysfunction caused by the toxic effect of protein bodies on the epithelial structures of the renal tubules, which in turn causes the phenomenon of dystrophy, Fanconi syndrome, and renal amyloidosis, has been clinically confirmed.
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Bence Jones protein in urine
The presence of protein in urine is called proteinuria. Prerenal proteinuria is understood as the presence of a huge amount of low-molecular protein in urine. In this case, there is no damage to the renal filter and tubules, and normal kidney function is not able to ensure the reabsorption of protein bodies. Extrarenal (false) proteinuria, i.e. occurring without impairment of kidney function, indicates the presence of an infectious or malignant process in the body. Proteinuria is observed in 60-90% of cases of patients with myeloma. About 20% of pathological conditions are Bence-Jones myeloma.
Bence-Jones protein in urine is differentiated due to humoral shifts in the β-immune system. The appearance of protein bodies is associated with myeloma pathology, paraproteinemic hemoblastoses, endotheliosis, Waldenstrom's macroglobulinemia, lymphatic leukemia, osteosarcomas. Detection of Bence-Jones protein in urine is an important diagnostic and prognostic step. Due to its low molecular weight, Bence-Jones protein is excreted in urine, damaging the epithelium of the renal tubules, which is fraught with the development of renal failure, which can lead to death. Timely classification of the protein according to the type is also important: λ-protein has a greater nephrotoxic effect than κ.
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Bence Jones Protein Assay
The presence of protein bodies other than serum in urine indicates lymphatic leukemia, osteosarcoma or myeloma (tumor processes of the bone marrow). Bence-Jones protein, when the urine filtrate is heated to 45-60º C, precipitates as a turbid sediment that settles on the walls of the test tube. A further increase in temperature to boiling values dissolves the separated turbidity.
The quantitative assay for Bence Jones protein is performed as follows:
- using part water and part nitric acid as a reagent;
- placing nitric acid (0.5-1 ml) in a test tube with layering of the same level of urine being tested;
- evaluation of the result after 2 minutes (the appearance of a thin ring at the boundary of liquid media indicates the presence of 0.033% protein bodies).
Observation of a thread-like ring requires diluting urine with water in a 1:1 ratio, the appearance of a thick ring indicates the need to mix part of the urine with three parts of water, and in the case of a compact ring, a portion of urine is diluted with seven portions of water. Moreover, dilution continues until the characteristic sediment appears in the 2-3rd minute of testing.
The amount of protein contained is calculated by multiplying 0.033% by the dilution value. For example, urine was diluted 10 times, the ring of protein bodies appeared at the end of the 3rd minute of study, then the percentage inclusion of protein is calculated as follows: 0.033x10=0.33.
If there is no sediment, the degree of turbidity is assessed - pronounced, weak or barely distinguishable traces of turbidity.
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Bence Jones protein secretion
Depending on the type of secreted immunoglobulin, a distinction is made between:
- light chain pathologies (Bence Jones protein secretion);
- glomerulopathy (secretion of other immunoglobulins).
Various combinations of kidney damage are also possible. As practice shows, nephropathy is a consequence of lymphoproliferative pathology (multiple myeloma, chronic lymphocytic leukemia, Waldenstrom's disease, etc.).
When released into the bloodstream, like all proteins with a molecular weight of up to 40 kDa, light chains bypass the renal filter, then break down into oligopeptides and amino acids via lysosomes. Excess light chains provoke dysfunction of the catabolism reaction and possible release of lysosomal enzymes, which entails necrosis of tubular tissue. Protein bodies lead to inability to reabsorb, and when monoclonal light chains combine with Tamm-Horsfall protein, protein cylinders are formed in the distal tubules.
Bence Jones protein in myeloma disease
Multiple myeloma is a pathological condition in which the body produces light immunoglobulin chains instead of full-fledged ones. Diagnosis of the disease and monitoring of the condition are carried out by laboratory testing of urine, which shows the quantitative content of protein bodies. The specification of the myeloma subtype is based on the analysis of blood serum. Clinical signs of the disease include: bone pain syndrome, urination dysfunction, hematomas of unknown origin, fluid retention in the body.
Bence Jones protein in myeloma is detected based on standard testing that shows the quantitative content of protein bodies and assesses the degree of kidney damage. Identification of the protein in the urine explains the damage to the epithelium with sclerosis of the renal stroma, which over time forms renal failure - a common cause of death as a result of myeloma damage (Bence Jones protein completely clogs the tubules, preventing urination).
Statistical data indicate that myeloma is differentiated in men over 60 years of age, with a history of genetic predisposition, suffering from obesity and immunosuppression, and also having been exposed to toxic and radioactive substances.
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Determination of Bence Jones protein
To differentiate a specific protein, a laboratory study of the average portion of morning urine is carried out (a volume of at least 50 ml is required). The presence of Bence-Jones protein with the determination of the quantitative component is possible by the immunofixation method. Separation of proteins occurs by electrophoresis with subsequent immunofixation using special serums. When binding the protein with antibodies of light and heavy chains of immunoglobulins, immune complexes are formed, which are assessed by staining.
It should be noted that even the minimum concentration of protein is detected due to the precipitation reaction to sulfosalicylic acid. Bence-Jones protein is determined by combining filtered urine (4 ml) with acetate buffer (1 ml). Subsequent heating to 60º C in a water bath and holding for 15 minutes with a positive sample produces a characteristic sediment. This method is considered the most reliable. An excessively acidic or alkaline environment and low relative density of urine can negatively affect the results of the analysis.
Research methods in which Bence-Jones protein is dissolved by heating to 100º C or precipitated again upon cooling are unreliable, since not all protein elements have the corresponding characteristics. But the use of indicator paper is completely unsuitable for detecting Bence-Jones protein.