Immunoglobulins, Free Light Chains, Serum

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Subject: Immunoglobulins, Free Light Chains, Serum

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Definition

  • Plasma cells do not produce complete immunoglobulin molecules. Instead, they produce the heavy and light chain components separately and then assemble them before secretion into the bloodstream. Because plasma cells usually make slightly more light chain components, there are usually some leftover light chains that are secreted in the blood without being bound to a heavy chain. These are known as serum free light chains (FLCs). Normally, there are only very low levels of free light chains in the blood (serum).

  • The Freelite, free kappa and free lambda light chain assays, are a new, highly sensitive aid in the diagnosis and monitoring of patients with multiple myeloma and related plasma cell disorders. The Freelite serum free kappa and free lambda light chain assays are run on serum and not on urine with increased sensitivity over current electrophoretic assays.

  • Recent studies have shown that Freelite serum free kappa and lambda light chain assays:

    • Detect up to 82% of nonsecretory myeloma

    • Detect and monitor AL amyloid patients, including those with no monoclonal protein by immunofixation (IFE)

    • Detect and assess response to treatment in >95% of patients with light chain and intact Ig multiple myeloma

    • Detect up to 96% of intact immunoglobulin myeloma patients

    • Provide an earlier marker of therapeutic response or resistance, compared to whole immunoglobulin/M spike assays

    • Evaluate risk of progression to myeloma in patients with monoclonal gammopathy of undetermined significance (MGUS)

    • In combination with serum protein electrophoresis or IFE alone, provide the optimal detection rate for all paraproteins

  • Normal range:

    • Free kappa: 3.30–19.40 mg/L

    • Free lambda: 5.71–26.30 mg/L

    • Kappa/lambda ratio: 0.26–1.65

Use

  • Diagnosis and monitoring progress of patients with nonsecretory myeloma and oligosecretory (<1 g/dL monoclonal protein in the serum and <200 mg/day monoclonal protein in the urine) myeloma

  • Diagnosis and monitoring progress of patients with light chain myeloma as well as primary systemic amyloidosis, in whom the underlying clonal plasma cell disorder may otherwise be difficult to detect and monitor

  • Predicting risk of progression of MGUS

  • Predicting risk of progression of solitary bone plasmacytoma

  • Diagnosis, monitoring during and after treatment, and perhaps prognosis of patients with multiple myeloma and an intact immunoglobulin

Interpretation (Table 16.45)

 
TABLE 16–45
Interpretation of Serum Free Light Chain Assays in Serum

Increased In (see Limitations)

  • Multiple myeloma

  • Lymphocytic neoplasms

  • Waldenström macroglobulinemia

  • Amyloidosis

  • Light chain deposition disease

  • Connective tissue diseases such as SLE

  • Renal impairment (common)

  • Overproduction of polyclonal free light chains (FLCs) from inflammatory conditions (common)

  • Biclonal gammopathies of different FLC types (rare)

Decreased In

  • Bone marrow function impairment

Limitations

  • Elevated kappa and lambda FLC may occur due to polyclonal hypergammaglobulinemia or impaired renal clearance. A specific increase in FLC (e.g., FLC kappa/lambda ratio) must be demonstrated for diagnostic purposes.

Suggested Readings

Bradwell  AR. Serum Free Light Chain Analysis, 2nd ed. Birmingham, UK: The Binding Site Ltd; 2005:13–21.
Katzmann  JA, Clark  RJ, Abraham  RS Serum reference intervals and diagnostic ranges for free κ and free λ immunoglobulin light chains: Relative sensitivity for detection of monoclonal light chains. Clin Chem.  2002;48:1437–1444.
 
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