Serum Free Light Chain Specificity and Sensitivity: A Reality Check

Abstract

In 2001, a commercial test consisting of 2 separate measurements to quantify κ and λ free light chains (FLCs) was reported in Clinical Chemistry (1). The antisera specificities in this assay were reported to be 10 000-fold higher for FLCs than for light chains bound to immunoglobulin heavy chains. FLCs were thought to be associated with imbalances in heavy and light chain production in monoclonal plasma cell populations, and their quantifiability in the presence of the bulk of serum immunoglobulin opened new opportunities for characterizing plasma cell proliferation disorders. The reference interval for polyclonal FLCs was documented, and the reference interval for the free light chain κ-to-λ (FLC K/L) ratio was demonstrated to be a sensitive indicator for excess (e.g., clonal) FLC production(1)(2). The gold standard for detection of monoclonal proteins is immunofixation electrophoresis (IFE). Several retrospective studies, however, showed that serum FLC had substantially higher detection limits than serum and urine IFE for diagnosis of the monoclonal light chain diseases of primary light-chain amyloidosis(3)(4) and light chain deposition disease(2), as well as nonsecretory multiple myeloma(5). This increase in diagnostic detection limit for this subset of monoclonal gammopathies indicates that the serum FLC assay is a natural addition to serum and urine IFE for diagnostic testing in the monoclonal gammopathies. The serum FLC assay specificity for the monoclonal plasma cell proliferative disorders resides in the …