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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]
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]
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]
[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).
Rather, they overexpress a monoclonal, aberrant free κ (i.e. kappa) or λ (i.e., lambda) immunoglobulin light chain. For diagnosis, the κ and λ free light chains are quantified by immunological methods and the ratio of κ to λ light chains is used to detect unbalanced light chain synthesis that is indicative of a monoclonal light chain ...
It is important in quantification of free light chains in diseases such as multiple myeloma. Quantification is important for disease classification and for disease monitoring once a patient has been treated (increased skewing of the ratio between kappa and lambda light chains after a patient has been treated is an indication of disease recurrence).
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.
In practice, this is inferred by the detection of only one of the mutually exclusive antibody light chains, kappa or lambda, on the entire population of the abnormal B cells. Normal B lymphocytes consist of a stew of different antibody-producing cells, resulting in a mixture of both kappa- and lambda-expressing cells.