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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. [39] An abnormal light-chain ratio has been defined as a kappa to lambda chain ratio of less than 0.26 or more than 1.65. [32]
Serum protein electrophoresis or immunofixation is positive in 67-100% of cases, while urine protein electrophoresis or immunofixation is positive in 50-100% of cases. [2] Serum free light chain measurement is positive in 100% of cases, evidence that the underlying monoclonal plasma cells secrete free light chains as well as heavy chains.
Light chain deposition disease can affect any organ. [3] Renal involvement is always present and can be identified by microscopic hematuria and proteinuria.Due to the gradual buildup of light chains from plasma filtration, renal function rapidly declines in the majority of patients with LCDD as either acute tubulointerstitial nephritis or rapidly progressing glomerulonephritis.
AL amyloidosis is caused by the deposition of abnormal antibody free light chains. The abnormal light chains are produced by monoclonal plasma cells, and, although AL amyloidosis can occur without diagnosis of another disorder, it is often associated with other plasma cell disorders, such as multiple myeloma and Waldenström's macroglobulinemia. [6]
Once set, light chain class remains fixed for the life of the B lymphocyte. In a healthy individual, the total kappa-to-lambda ratio is roughly 2:1 in serum (measuring intact whole antibodies) or 1:1.5 if measuring free light chains, with a highly divergent ratio indicative of neoplasm. The free light chain ratio ranges from 0.26 to 1.65. [1]
Serum protein electrophoresis showing a paraprotein (spike/peak in the gamma zone) in a patient with multiple myeloma.. A myeloma protein is an abnormal antibody (immunoglobulin) or (more often) a fragment thereof, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells, typically in multiple myeloma or Monoclonal gammopathy of ...
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[70] [79] These biomarkers are >60% clonal plasma cells, a serum involved / uninvolved free light chain ratio ≥ 100 (the concentration of the involved free light chain must be ≥ 100 mg/L) and more than one focal lesion ≥ 5 mm by MRI. [70] [79] Together, these biomarkers and the CRAB criteria are known as myeloma-defining events (MDEs).