Introduction
Bence Jones protein might appear to be a small detail from 1847, but for someone working in a medical lab, it is one of the most significant findings they can encounter. Discovered by Henry Bence Jones, this unique type of protein found in urine serves as an important early indicator of serious blood disorders, like multiple myeloma. In this article, you will learn about what Bence Jones protein is, how it is detected in a laboratory, the possible causes of protein appearing in urine, and the role of tests such as the urine protein to creatinine ratio in the overall diagnostic process.
Table of Contents
What Is Bence Jones Protein?
Bence Jones protein refers to free immunoglobulin light chains, either kappa (κ) or lambda (λ), that are made in large amounts by abnormal plasma cells and released into the urine. In a healthy person, these light chains are produced in equal amounts and usually do not appear in urine in noticeable amounts.
When plasma cells become cancerous, as in multiple myeloma or Waldenström’s macroglobulinemia, they produce excessive amounts of free light chains.
These proteins are small in size, typically ranging from 22 to 44 kilodaltons, which allows them to pass through the glomerular filtration barrier easily and enter the urine.
Classic Thermal Property
Bence Jones protein precipitates at 40–60°C and redissolves at 100°C. This distinctive heat behaviour was historically used for bedside detection. Modern electrophoresis methods have replaced this test, but understanding it deepens your clinical reasoning.
What Causes Protein in Urine? A Clinical Overview
What Causes Protein in Urine? A Clinical Overview
Understanding the causes of protein in urine is essential for every laboratory professional.
Proteinuria can occur through four main mechanisms, each reflecting a different underlying condition
Bence Jones proteinuria is a typical example of overflow proteinuria.
In this case, the kidneys are not necessarily damaged; instead, the high levels of free light chains overwhelm the kidneys’ ability to reabsorb them. This distinction significantly affects how the condition is managed clinically.
Laboratory Diagnosis of Bence Jones Protein
A structured method for laboratory diagnosis is crucial. The following process describes the step-by-step procedure starting from the initial screening to the final confirmation tests.
Step 1: Initial Urine Screening
The first step in investigating a case where proteinuria is suspected is to perform a routine urinalysis.
However, medical laboratory technology students should be aware of a key limitation: the standard urine dipstick test only detects albumin and does not identify Bence Jones protein or other light chains. As a result, a patient with significant Bence Jones proteinuria may receive a completely false-negative result from a dipstick test.
The sulfosalicylic acid (SSA) turbidity test is a simple, fast, and affordable test that can detect all types of proteins, including light chains.
If the SSA test shows a cloudy precipitate while the dipstick result is negative, this combination is a classic sign that further testing should be conducted to check for Bence Jones protein.
Key Alert for MLT Students
If the dipstick test is negative but the SSA test is positive, you should immediately check for Bence Jones protein.
Do not ignore proteinuria just because the dipstick result is negative.
Step 3: Urine Protein Electrophoresis (UPEP)
The urine protein electrophoresis (UPEP) is the main method used to detect Bence Jones protein.
A concentrated urine sample is placed on an agarose gel or a capillary electrophoresis system, and the proteins are separated into different groups based on their electrical charge and size.
A discrete M-spike (monoclonal band) in the gamma or beta region on UPEP strongly suggests the presence of a paraprotein. The absence of a band does not exclude light chain disease, as very small quantities may be missed — immunofixation is needed for confirmation.
Step 4: Immunofixation Electrophoresis (IFE)
Immunofixation electrophoresis (IFE) is the main method used to confirm the presence of Bence Jones protein. Following urine protein electrophoresis (UPEP), specific antibodies are applied to the gel that target IgG, IgA, IgM, kappa (κ), and lambda (λ) light chains. The presence of a visible band when using anti-κ or anti-λ antibodies, but not with antibodies against heavy chains, indicates the presence of free light chains.
IFE is 10 to 100 times more sensitive than UPEP and can identify monoclonal proteins even when they are present in very small amounts.
It also determines the exact type of light chain, which is important for predicting the course of the disease and choosing the right treatment for myeloma.
Step 5: Free Light Chain (FLC) Assay
The serum free light chain (FLC) assay (e.g., Freelite®) is a nephelometric or turbidimetric immunoassay that quantifies free κ and λ light chains in serum — and can also be performed on urine. Key reference values:
- Serum free kappa: 3.3–19.4 mg/L
- Serum free lambda: 5.7–26.3 mg/L
- Normal kappa/lambda ratio: 0.26–1.65
- An abnormal ratio (>1.65 or <0.26) indicates a monoclonal light chain excess and supports diagnosis of myeloma or related plasma cell disorders
Step 6: Urine Protein to Creatinine Ratio (UPCR) Test
The urine protein to creatinine ratio (UPCR) test offers a fast and dependable way to estimate how much protein is being lost in the urine, using a single random urine sample. This method is more convenient than collecting a 24-hour urine sample. In non-pregnant adults, a UPCR result higher than 0.2 mg/mg is considered abnormal. Although the UPCR test is helpful for tracking glomerular diseases, it is not a replacement for urine protein excretion profile (UPEP) and immunofixation electrophoresis (IFE) when Bence Jones proteinuria is suspected, because it does not determine the type of protein being excreted.
Laboratory Workflow Summary
Dipstick / SSA → 24-hour urine collection → UPEP (screening) → IFE (confirmation) → FLC assay (quantification and monitoring). Each step adds diagnostic certainty.
Protein Trace in Urine in Pregnancy
Protein in the urine during pregnancy is often seen and usually not a cause for concern. It may happen due to the increased rate at which the kidneys filter blood or because of vaginal secretions mixing with the urine. However, if there is ongoing proteinuria of 300 mg or more in a 24-hour period after 20 weeks of pregnancy, it is considered a sign of preeclampsia, which is a serious condition involving high blood pressure.
Finding Bence Jones protein during pregnancy is very rare and would require immediate medical tests related to the blood and blood cells.
It is important to consider the results of the urine test along with the overall health condition and how far along the pregnancy is before making any conclusions.
Will Drinking Water Reduce Protein in Urine?
Patients often ask this question. The short answer is that it depends entirely on the cause. If the proteinuria is mild and temporary, such as from dehydration or strenuous exercise, drinking enough water can help bring urinary protein levels back to normal. However, in cases of underlying disease — like nephrotic syndrome or Bence Jones proteinuria — simply drinking more water won’t treat the actual problem. It may only make the urine sample appear less concerning than it is. To effectively lower protein in the urine, it is essential to address the underlying condition. This may involve immunotherapy for myeloma, ACE inhibitors for diabetic nephropathy, or antihypertensive medications for preeclampsia.
Clinical Significance of Bence Jones Protein
5. Diagnosis of Multiple Myeloma: Found in ~60–80% of myeloma patients. Urine light chains are part of the CRAB diagnostic criteria (hyperCalcaemia, Renal failure, Anaemia, Bone lesions).
6. Disease Monitoring: Serial light chain measurements by FLC assay or urine IFE track response to chemotherapy or immunotherapy over time.
7. Renal Risk Assessment: Free light chains are directly nephrotoxic. High urinary levels predict cast nephropathy (myeloma kidney), a reversible but dangerous complication.
8. Prognosis: Kappa vs. lambda type, and quantitative load of light chains, correlate with disease severity and patient survival outcomes.
9. AL Amyloidosis Detection: Light chain deposition in the heart, kidneys, and nerves can accompany Bence Jones proteinuria and requires prompt diagnosis.
Key Takeaways
• Bence Jones protein refers to free immunoglobulin light chains (either κ or λ) produced by malignant plasma cells, which is a key feature of multiple myeloma.
• A routine urine dipstick test is not able to detect Bence Jones protein.
The initial screening method is the serum free light chain (SSA) test, while urine protein electrophoresis (UPEP) combined with immunofixation (IFE) is considered the gold standard for confirming the presence of Bence Jones protein.
• The laboratory process for diagnosing Bence Jones protein follows a specific sequence: starting with the SSA test, followed by a 24-hour urine collection, then UPEP and IFE, and finally the free light chain (FLC) assay.
• The urine protein to creatinine ratio test is helpful for detecting proteinuria but does not identify the type of protein present.
Electrophoresis is necessary to determine the specific type of protein.
• Drinking water alone cannot treat proteinuria caused by an underlying disease.
The only effective approach is to identify and address the underlying cause of the proteinuria.
• An abnormal ratio of kappa to lambda light chains on the FLC assay is a sensitive early sign of the growth of monoclonal plasma cells.
