Free κ and λ Light Chains Plus Ratio, Quantitative

Serum

0.5 mL

0.2 mL

Red-top tube or gel-barrier tube

Free light chain (FLC) results should be considered under the following categories and investigated appropriately (κ = kappa free light chain; λ = lambda free light chain).

1. Normal samples: Serum κ, λ, and κ:λ are all within the normal ranges. If accompanying serum electrophoretic tests are normal, it is most unlikely that the patient has a monoclonal gammopathy.

2. Abnormal κ:λ ratios: Support the diagnosis of a monoclonal gammopathy and require an appropriate tissue biopsy. Borderline elevated κ:λ ratios occur with renal impairment and may require appropriate renal function tests.

3. Low concentrations of κ, λ, or both: Indicate bone marrow function impairment.

4. Elevated concentrations of both κ and λ with a normal κ:λ ratio: May be due to the following:

• Renal impairment (common)

• Overproduction of polyclonal FLCs from inflammatory conditions (common)

• Biclonal gammopathies of different FLC types (rare)

5. Elevated concentrations of both κ and λ with an abnormal κ:λ ratio: Suggest a combination of monoclonal gammopathy and renal impairment.

Turbidimetric

• Free κ light chains: 3.3−19.4 mg/L

• Free λ light chains: 5.7−26.3 mg/L

• κ:λ free light chain ratio: 0.26−1.65

Immunoglobulin molecules consist of two identical heavy chains (α, δ, ε, γ, or μ) that define the immunoglobulin class and two identical light chains (κ or λ). Each light chain is covalently linked to a heavy chain and the two heavy chains are linked covalently at the hinge region. In healthy individuals, the majority of light chains in serum exists in this form, bound to heavy chain; however, low levels of free light chain (FLC) are found in serum of normal individuals due to the overproduction and secretion of FLC by the plasma cells. While the molecular weight of both light chains is approximately 22.5 kilodaltons, in serum, κ free light chain (κ-FLC) exists primarily as a monomer and λ free light chain (λ-FLC) as a covalently-linked dimer with a molecular weight of approximately 45 kilodaltons. This will lead to a differential glomerular filtration rate for κ-FLC and λ-FLC and may explain the observed ratio of κ-FLC to λ-FLC of 0.625 in serum compared to the ratio of bound κ to λ of 2.0.

FLC levels in urine are low. In a healthy kidney, the tubular cells selectively reabsorb all FLC so their presence in urine is probably due to secretion into the urinary tract.

Elevated serum levels of monoclonal FLC are associated with malignant plasma cell proliferation (eg, multiple myeloma), primary amyloidosis, and light chain deposition disease. Raised serum levels of polyclonal FLC may be associated with autoimmune diseases such as systemic lupus erythematosus. The appearance of higher levels of FLC in urine may be indicative of kidney disease or malignant lymphoproliferative disease such as multiple myeloma. The monoclonal urinary FLC associated with lymphoid malignancy is called a Bence Jones protein.