What are Bence Jones proteins and how are they diagnosed, and what symptoms are associated with them?

Bence Jones Proteins: Definition, Diagnosis, and Clinical Manifestations

What Are Bence Jones Proteins?

Bence Jones proteins are monoclonal immunoglobulin free light chains (either kappa or lambda) that appear in the urine and serve as a critical diagnostic marker for plasma cell disorders, particularly multiple myeloma and related conditions. 1

These proteins represent abnormal production by clonal plasma cells and indicate underlying B-cell dyscrasia. Approximately 15-20% of multiple myeloma patients secrete only monoclonal light chains without intact immunoglobulin heavy chains, constituting light-chain multiple myeloma. 2

Diagnostic Methods

Primary Diagnostic Approach

The gold standard for detecting Bence Jones proteins is 24-hour urine collection with protein electrophoresis and immunofixation. 1 This method allows both identification of the monoclonal light chain type (kappa vs lambda) and quantification of protein excretion. 1

Serum-Based Testing

• Serum free light chain (FLC) assay by immunoturbidimetry demonstrates 100% sensitivity for detecting Bence Jones myeloma and can identify all patients with light-chain myeloma. 3, 4
• The serum FLC ratio (kappa/lambda) provides crucial diagnostic information, with abnormal ratios (<0.26 or >1.65) indicating monoclonal light chain production. 1
• Serum FLC testing is superior to urine testing for monitoring disease, as urine may become falsely negative in 32% of patients while serum remains abnormal. 4

Diagnostic Criteria Thresholds

• Active myeloma: Bence Jones protein >2500 mg/24 hours 1
• Smoldering myeloma: Bence Jones protein ≥500 mg/24 hours without end-organ damage 1
• Light-chain smoldering myeloma: ≥0.5 g/24 hours urinary excretion OR ≥10% bone marrow plasma cells 2

Important Diagnostic Pitfall

High-resolution electrophoresis may detect multiple light chain bands in patients with tubular proteinuria who do NOT have myeloma. 5 This polyclonal light chain pattern (particularly kappa bands) can be mistaken for Bence Jones protein. The key distinction is that true Bence Jones protein shows monoclonal (single clone) light chains, while tubular proteinuria shows polyclonal (multiple clones) light chains. 5

Clinical Manifestations and Associated Symptoms

Renal Manifestations

• Renal insufficiency (creatinine >2 mg/dL or creatinine clearance <40 mL/min) is a cardinal feature of active myeloma with Bence Jones proteinuria. 1
• Light chain cast nephropathy requires immediate treatment due to risk of irreversible kidney damage. 6
• The nephrotoxic effect is concentration-dependent, with higher levels causing more significant renal injury. 6

Hematologic Manifestations

• Anemia (hemoglobin <10 g/dL or >2 g/dL below normal) occurs due to bone marrow infiltration by plasma cells. 1
• Suppression of normal immunoglobulin production leads to secondary immunodeficiency with recurrent infections. 1, 3
• Median levels of IgG, IgA, and IgM are significantly reduced compared to normal individuals. 3

Skeletal Manifestations

• Osteolytic bone lesions on skeletal radiography, CT, or PET-CT 1
• Hypercalcemia (calcium >11 mg/dL or >1 mg/dL above upper limit of normal) from bone destruction 1
• Pathologic fractures and severe osteopenia 1

Systemic Manifestations

• Elevated β2-microglobulin and C-reactive protein indicating inflammatory syndrome 3
• Hyperviscosity syndrome in some cases 1
• AL amyloidosis can develop, with 7% of patients with idiopathic Bence Jones proteinuria progressing to this complication 2

Risk Stratification and Prognosis

Patients with light-chain smoldering myeloma (≥0.5 g/24h urinary excretion or ≥10% bone marrow plasma cells) have a 27.8% risk of progression at 5 years, 44.6% at 10 years, and 56.5% at 15 years. 2

High-risk features for progression include: 1, 2

• Markedly abnormal serum FLC ratio (<0.01 or >100)
• Higher urinary M-protein excretion
• Increased bone marrow plasma cell percentage
• Reduction of all three uninvolved immunoglobulins
• Elevated serum creatinine

Monitoring Recommendations

For patients with smoldering myeloma and Bence Jones proteinuria, perform blood and urine analysis every 3-6 months, with bone studies annually or as clinically indicated. 6 This surveillance strategy allows early detection of progression to active disease requiring treatment.