In recent decades, measuring the amount of free light chains (FLCs) in the blood has become a practical clinical test.
Each immunoglobulin light-chain molecule contains approximately 220 amino acids in a single polypeptide chain that is folded to form constant and variable region domains.
[2] The production of free immunoglobulin light chains in normal individuals is approximately 500 mg/day from bone marrow and lymph node cells.
This may simply be to allow for the proper structure of the intact immunoglobulin molecules, but it is also possible that free light chains have an immunological function.
It is very efficient and can process 10–30 g of low-molecular-weight proteins per day, so under normal conditions no light chains pass beyond the proximal tubules.
Conversely, urine concentrations of free light chains could increase if renal function improved in a multiple myeloma patient receiving treatment.
[17][18][19][20] The 500 mg of FLCs produced per day by the normal lymphoid system, however, flows through the glomeruli and is completely processed by the proximal tubules.
If the proximal tubules of the nephrons are damaged or stressed (such as in hard exercise), filtered FLCs may not be completely metabolised and small amounts may then appear in the urine.
[18][19][20][31] A series of studies, principally from the Mayo Clinic, have indicated that patients with an abnormal free kappa to free lambda ratio have an increased risk of progression to active myeloma from precursor conditions including monoclonal gammopathy of undetermined significance (MGUS),[32][33] smouldering myeloma[34] and solitary plasmacytoma of the bone.
[35] Abnormal free light chain production has also been reported to be prognostic of a worse outcome in multiple myeloma[36][37][38] and chronic lymphocytic leukaemia.
[41] Other guidelines for the use of serum free light chain measurement in the management of AL amyloidosis,[42] plasmacytoma[43] and the comparison of treatment responses in clinical trials[44] have also been published.