What are Bence Jones proteins?

Bence Jones Proteins: Definition and Clinical Significance

Bence Jones proteins are monoclonal immunoglobulin free light chains that appear in the urine of patients with plasma cell disorders, serving as an important diagnostic marker for multiple myeloma and related conditions. 1

Definition and Characteristics

• Bence Jones proteins are specifically monoclonal light chains of immunoglobulins that can be detected in urine, indicating the presence of a plasma cell dyscrasia or other B-cell related disorders 1, 2
• These proteins represent the earliest known biological markers of malignant cell dyscrasia and are named after Henry Bence Jones who first described them in the 1800s 2
• They can be kappa or lambda light chain isotypes and may appear as monomers or dimers in urine samples 3

Clinical Significance

• Bence Jones proteins are crucial diagnostic markers for:

  • Multiple myeloma (particularly light-chain multiple myeloma) 4
  • Waldenström's macroglobulinemia 5
  • Light chain amyloidosis (AL) 1, 6
  • Other lymphoproliferative disorders 2

• The presence of Bence Jones proteins ≥500 mg/24h is one of the diagnostic criteria for smoldering multiple myeloma 4, 1

• In active multiple myeloma, Bence Jones protein excretion often exceeds 2500 mg/24h 4

Detection Methods

• The gold standard for detection is 24-hour urine collection with:

  • Protein electrophoresis 3, 5
  • Immunofixation to identify the specific light chain type (kappa or lambda) 3

• Newer methods include:

  • Serum free light chain (sFLC) assays, which can often replace urine tests for monitoring patients with light-chain multiple myeloma 7
  • Combined algorithms using serum free light chain ratios and difference between involved and uninvolved free light chains (dFLC) can reduce the need for urine testing by up to 42% 5

Prognostic Value

• The amount of Bence Jones protein excretion has prognostic significance:
  • Higher levels (≥0.5g/24h) are associated with increased risk of progression to symptomatic disease 6
  • Patients with light-chain smoldering multiple myeloma (defined by Bence Jones protein ≥0.5g/24h or ≥10% bone marrow plasma cells) have a cumulative probability of progression to active disease of:
    • 27.8% at 5 years
    • 44.6% at 10 years
    • 56.5% at 15 years 6

Clinical Pitfalls and Considerations

• False positives can occur with high-sensitivity techniques that may detect multiple light chain bands in patients without B-cell dyscrasia 3
• Polyclonal light chains can separate into multiple bands that may be confused with Bence Jones proteins 3
• Tubular proteinuria of any etiology can produce patterns that mimic Bence Jones proteins 3
• Serum free light chain assays may remain abnormal even when urine tests become negative during treatment monitoring 7

Monitoring and Management

• For patients with smoldering multiple myeloma with Bence Jones proteins, monitoring should include:
  • Blood and urine analysis every 3-6 months
  • Annual bone studies or as clinically indicated 1
• The presence of Bence Jones proteins causing renal damage (cast nephropathy) requires immediate treatment 1
• Treatment decisions should be based on the underlying condition:
  • Active multiple myeloma requires complete antimyeloma therapy 1
  • Smoldering multiple myeloma typically requires observation without immediate treatment 1