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Lambda light chain
(Free Light Chain Assay – Essential Marker for Myeloma, MGUS, AL Amyloidosis & Renal Handling)
Synonyms
- Lambda free light chain (λ-FLC)
- Free λ light chain
- Serum free lambda light chain
- λ immunoglobulin light chain
- Lambda monoclonal protein
- Bence–Jones lambda protein (urine)
Units of Measurement
- g/L
- mg/dL
- mg/100 mL
- mg%
- mg/mL
Key Conversions
1 mg/dL = 0.01 g/L
1 mg/mL = 1 g/dL = 10 g/L
mg% = mg/dL = mg/100 mL
Free λ chains are measured in mass units, not in molar units.
Description
Lambda (λ) light chains are immunoglobulin light chains produced by normal plasma cells in slightly smaller amounts than kappa chains.
When not attached to heavy chains, they circulate freely as:
- Free lambda light chains (FLC)
These are:
- Filtered by kidneys
- Reabsorbed by proximal tubules
- Eliminated via urine (Bence–Jones proteins)
Serum λ FLC measurement is a cornerstone in evaluating:
- Multiple myeloma
- Light chain myeloma
- MGUS
- AL amyloidosis
- Monoclonal gammopathies
- Renal involvement in plasma cell disorders
Physiological Role
Normal Production
Plasma cells produce λ light chains at a slightly lower rate than κ:
- Normal κ:λ ratio ~0.26–1.65
- Both increase in inflammation or renal impairment (ratio stays normal)
Renal Handling
- Free λ chains are cleared by glomeruli
- Catabolized in proximal tubules
- Rise markedly in kidney failure
Clinical Significance
HIGH Lambda Light Chain
Clinically most important finding.
1. Multiple Myeloma (MM) – λ Restricted
- Elevation of λ FLC
- Abnormal κ/λ ratio (very low)
- λ monoclonal spike on immunofixation
- May be light-chain only with little/no M-spike
2. AL Amyloidosis (λ Type)
~75% cases involve λ light chains.
Findings:
- Elevated free λ
- Abnormal ratio
- Organ dysfunction (heart, kidney, nerves)
3. MGUS
Milder λ elevation with abnormal κ/λ ratio.
4. Renal Impairment
Reduced clearance → λ and κ both increase
Ratio remains normal unless true monoclonal production.
5. Autoimmune/Inflammatory Conditions
Mild polyclonal λ elevation.
LOW Lambda Light Chain
Rarely clinically significant alone.
Causes:
- Immune suppression
- Chemotherapy
- Plasma cell aplasia
- Suppression by dominant κ clone (in κ-restricted myeloma)
Reference Intervals
(IMWG + Mayo + ARUP + Tietz 8E)
Assay ranges may vary; these are standard nephelometry/turbidimetry values.
Adults
- Free λ Light Chain: 5.7 – 26.3 mg/L
(= 0.0057 – 0.0263 g/L)
κ/λ Ratio
- Normal ratio: 0.26 – 1.65
- λ-restricted disease → ratio < 0.26
Renal Reference Range
Kidney failure elevates both chains:
- λ typically: 10 – 65 mg/L
- Ratio still usually 0.37 – 3.1
Myeloma Diagnostic Cutoffs
- λ > 100 mg/L with abnormal ratio → monoclonal λ process
- κ/λ ratio < 0.01 highly specific for λ myeloma
Diagnostic Uses
1. Multiple Myeloma
- Elevated λ FLC
- Abnormally low κ/λ ratio
- Bone marrow plasmacytosis
- Useful in oligosecretory/non-secretory cases
2. AL Amyloidosis
λ elevation strongly associated with amyloid fibril formation.
3. MGUS & Smoldering Myeloma
λ deviation indicates monoclonal proliferation.
4. Renal Insufficiency
- λ increases due to reduced filtration
- Must use renal reference range for interpretation
5. Monitoring Treatment
Chemotherapy response assessed by fall in λ FLC.
6. Relapse Detection
Early rise in λ predicts recurrence.
7. Urine Studies
Detect Bence–Jones λ proteins in myeloma/amyloidosis.
Analytical Notes
- Use serum (not plasma)
- Avoid hemolysis
- Free light chain assays vary by manufacturer (Freelite®, N-Latex)
- Renal impairment influences absolute levels → use ratio
- Always interpret with SPEP, UPEP, and immunofixation
Clinical Pearls
- κ/λ ratio is the key discriminator, more than absolute values.
- In renal failure, λ rises but ratio usually remains normal unless monoclonal.
- λ free light chain myeloma often presents with renal failure from cast nephropathy.
- λ abnormalities are far more common in AL amyloidosis than κ.
- Serum FLC assay is more sensitive than urine for detecting light chain disease.
Interesting
Fact
Lambda chains normally exist as monomers, while kappa often form dimers - this difference partially influences their renal clearance patterns.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Immunoglobulins & FLC Testing
- International Myeloma Working Group (IMWG) - Light Chain Guidelines
- Mayo Clinic Laboratories - Free Lambda Light Chains
- ARUP Consult - Plasma Cell Dyscrasias
- Blood / Lancet Hematology - Free Light Chain Biology
- NIH / MedlinePlus - Light Chain Tests