New Perspectives on the Measurement of Free Light Chains in the Different Matrices: Serum, Urine, and Cerebrospinal Fluid

Dear Colleagues,

The determination of free light-chains (S-FLCs) in serum has been a turning point in the diagnosis, prognosis, and monitoring of monoclonal gammopathies of undetermined significance (MGUS), multiple myeloma (MM), and light-chain amyloidosis (AL). The method, established in the 2000s, quantifies serum-FLC using polyclonal antibodies to identify the presence and pattern of multiple myelomas in patients; meanwhile, the assays are nowadays more often based on monoclonal antibodies. Since the FLC are the isoforms, kappa (κ) and lambda (λ), of the light chains of immunoglobulins that circulate unbound in the serum, in order to facilitate the interpretation, the results of their quantities will be accompanied by a ratio. The calculated value of κ/λ free chains (FLC) relative to the reference intervals may indicate the presence of plasma cell dyscrasias in the patient, such as multiple myeloma or AL amyloidosis. In light of this, the International Myeloma Working Group (IMWG) has introduced the ratio of FLC into the SLiM criteria as a criterion of malignancy. IMWG also recommends examination of the urine. In fact,  FLC assays have been performed recently on different matrices other than serum, such as urine and cerebrospinal fluid analyses (CSF). In particular, the analysis of FLC in CSF have established their role as a biomarker for the diagnosis of multiple sclerosis (MS). To summarize, the purpose of this Special Issue is to offer an overview of the FLC assay principles, analytical performance, and the use of any new cutoffs that may be useful in the detection of the related pathologies. The Special Issue will also address the possible benefits of using the new generation FLC tests and new experimental approaches used in laboratories.

Dr. Massimo Pieri
Guest Editor

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• free light chain
• kFLC index
• plasma cell dyscrasias
• multiple sclerosis