Free κ and λ Light Chains Plus Ratio, Quantitative, Urine

Immunoglobulin molecules consist of two identical heavy chains (α, δ, ε, γ, or μ) which 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 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.

The laboratory will perform FLC analysis on urine, but a serum sample is preferred for many reasons. Analogous to glucose metabolism, FLC spill into the urine only after the tubular reabsorptive capacity is exceeded. Thus, the serum FLC ratio has been shown to be abnormal in patients with monoclonal gammopathy despite normal urine FLC ratios or normal urine immunofixation. Serum tests are also more sensitive for the detection of residual monoclonal FLC after treatment and for the early detection of monoclonal FLC after relapse in patients with monoclonal gammopathy.

FLC levels in urine are normally 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.

The appearance of higher levels of polyclonal FLC in urine may be indicative of kidney or autoimmune disease. An abnormal urine FLC ratio may be indicative of malignant lymphoproliferative disease such as multiple myeloma. The monoclonal urinary FLC associated with lymphoid malignancy is called a Bence-Jones protein.