What is Bence Jones Protein?
Bence Jones protein refers to monoclonal immunoglobulin free light chains (either kappa or lambda) that are detected in the urine of patients with plasma cell disorders and other B-cell malignancies. 1, 2
Definition and Clinical Significance
Bence Jones proteins are the earliest known biological markers of malignant plasma cell dyscrasia, representing unbound free light chains produced by clonal plasma cells or B-cells that are small enough to be filtered by the kidney and appear in urine. 3, 4
These proteins indicate the presence of monoclonal gammopathies and serve as a crucial diagnostic marker for multiple myeloma, Waldenström macroglobulinemia, light chain amyloidosis (AL), and other lymphoproliferative disorders. 2, 5
The term "Bence Jones protein" is used interchangeably with "monoclonal light chains" in urine in some countries. 1
How Detection Works
The gold standard for detecting Bence Jones proteins is 24-hour urine collection with protein electrophoresis and immunofixation, which allows both identification and quantification of the monoclonal light chains. 1, 2
Clonality is determined by detecting either kappa or lambda light chains exclusively (not both), which distinguishes monoclonal from polyclonal light chain excretion. 1
The serum free light chain (FLC) assay measures kappa and lambda independently, and an abnormal kappa:lambda ratio (normal 0.26-1.65) indicates clonality—a high ratio suggests kappa monoclonality while a low ratio suggests lambda monoclonality. 1, 2
Clinical Context and Disease States
Active (symptomatic) multiple myeloma is defined by Bence Jones protein >2,500 mg/24 hours along with evidence of end-organ damage. 1, 2
Smoldering (asymptomatic) myeloma is characterized by Bence Jones protein ≥500 mg/24 hours without end-organ damage, though these patients require close monitoring as they have a 27.8% risk of progression at 5 years. 2, 5
Monoclonal gammopathy of renal significance (MGRS) can occur when Bence Jones proteins cause kidney damage even in patients with low clonal burden who don't meet criteria for multiple myeloma. 1
Important Clinical Manifestations
Renal insufficiency (creatinine >2 mg/dL) is a cardinal feature when Bence Jones proteinuria is present, as these proteins are directly nephrotoxic and can cause light-chain cast nephropathy. 1, 2
Light-chain cast nephropathy is now considered a myeloma-defining event and requires immediate treatment. 1, 2
The type of light chain (kappa vs lambda), degree of polymerization, and isoelectric point of the molecule influence the clinical course and severity of kidney damage. 3, 4
Critical Diagnostic Pitfalls
Avoid relying on urine dipstick alone—standard dipsticks detect albumin but not light chains, so Bence Jones proteinuria can be missed entirely if only dipstick is used. 1
Polyclonal light chains can mimic Bence Jones protein on electrophoresis in patients with tubular proteinuria of any cause, potentially leading to false positive diagnoses; immunofixation is essential to distinguish monoclonal from polyclonal patterns. 6
Renal impairment affects serum free light chain ratios—the normal ratio expands to 0.34-3.10 in severe renal impairment (CKD stage 5), and different assays (FreeLite vs N Latex) are affected differently by kidney dysfunction and are mathematically inconvertible. 1
Monitoring Approach
For patients with light chain myeloma, serial 24-hour urine collections with total protein and electrophoresis to quantify Bence Jones proteinuria are recommended for treatment response assessment. 1
For smoldering myeloma with Bence Jones proteinuria, perform blood and urine analysis every 3-6 months with bone studies annually or as clinically indicated. 2, 5
The same assay method must be used consistently for a given patient throughout their monitoring and treatment to ensure accurate comparison. 1