Serum free light chains in clinical laboratory diagnostics

Abstract

Monoclonal free light chains (FLCs) are important disease biomarkers in patients with plasma cell-proliferative disorders. The increasing evidence for clonal diversity and evolution in multiple myeloma highlights the importance of laboratory algorithms that measure both intact immunoglobulins and monoclonal FLCs, at diagnosis and when monitoring response to treatment. A particular focus in the field has been on the utility of serum FLC (sFLC) assays to replace urine electrophoresis for monoclonal FLC measurement. Due to the limited sensitivity and practical constraints of urine analysis, a serum-based algorithm of SPE and sFLC has been adopted by many laboratories as a first line screen in patients with suspected monoclonal gammopathies. This review will discuss the data supporting the use of this simple serum-based algorithm at initial diagnosis, including its utility for the rapid identification of monoclonal FLC in the setting of unexplained acute kidney injury, and provide a comprehensive review of the diagnostic sensitivity of sFLC in patients with multiple myeloma, AL amyloidosis and light chain deposition disease.

Keywords: AKI; AL amyloidosis; Electrophoresis; Free light chains; IFE; IIMM; Immunoassays; LCDD; LCMM; MGUS; MM; Mabs; Multiple myeloma; NSMM; SPE; Serum protein; UPE; WM; Waldenström's macroglobulinaemia; acute kidney injury; immunofixation electrophoresis; intact immunoglobulin MM; kappa; lambda; light chain MM; light chain deposition disease; monoclonal antibodies; monoclonal gammopathy of undetermined significance; multiple myeloma; nonsecretory MM; ratio of κ sFLC to λ sFLC concentration; sFLC; sFLC κ/λ ratio; serum free light chain; serum protein electrophoresis; urine protein electrophoresis; κ; λ.