Free light chains
From Standard of Care
The kappa/lambda ratio of whole immunoglobulin molecules is 2 to 1, and the kappa/lambda ratio of free light chains is 1 to 1.5.
Lambda light chains occur as dimers whose serum half-life is approximately 3x longer than that of monomeric kappa light chains.
Excess production of kappa or lambda light chains alters the kappa/lambda ratio.
Monoclonal light chains are found in the serum of patients with myeloma, Waldenström’s macroglobulinemia, mu-heavy chain disease, primary amyloidosis, light chain deposition disease, monoclonal gammopathy of undetermined significance, and lymphoproliferative disease such as B-cell CLL.
Measurement of free light chain concentration in serum is useful for diagnosis, prognosis, monitoring disease activity and following response to therapy of these disorders.
With chronic infection and chronic inflammatory states and renal insufficiency, there may be a diffuse increase in both kappa and lambda free light chains, but the kappa/lambda ratio remains in the normal limits.
Secretion of kappa and lambda free light chains by the total body plasma cell pool is about 1 g per day.
Free light chains all mostly cleared through the renal glomeruli, with a serum half-life of 2-4 hours.
Free light chains and not detectable in the urine of healthy individuals because they are metabolized in the proximal tubules of the nephron.
Serum concentration of free light chains increases with age > 60 and may reach 50 mg/liter in those 70-80 years of age and the kappa/lambda ratio remains within normal limits.
Serum concentrations depend on the balance between production by plasma cells and renal clearance.
Serum free light chains cleared rapidly through the renal glomeruli, with a serum half life of 2-4 hours and are then metabolized in the proximal tubules of the nephron.
Normally little protein escapes into the urine and serum free light chains must increase signficantly before it can overwhelm the absorption mechanisms of the kidney.
Normal plasma cell production of free light chain is 0.5-1 gm per day.
The kidneys can metabolize 10-30 gm of free light chains daily.
Abnormal concentrations of kappa and lambda free light chains may be a result of immune stimulation, immune suppression, reduced renal clearance or plasma cell proliferative disorders.
Serum from patients with polyclonal hypergammaglobulinemia or renal insufficiency often have elevated kappa and lambda free light chains related to increased synthesis or reduced renal clearance: but in such disorders the ratio of kappa/lambda free light chain ration remains normal.
FLCs are detected by electrophoresis of concentrated urine followed by immunofixation confirming protein bands as kappa or lambda FLCs.
Quantification of urinary total protein and FLC excretion is performed by densitometer tracing on a 24 hour urine collection or calculated via urine creatinine on a random sample of urine.