Abnormal Serum Free Light Chain Ratios in the Absence of Clonal Plasma Cell Disease: A Review of the Literature

The serum free light chain (sFLC) κ/λ ratio is an important component of laboratory evaluation of plasma cell disorders and is incorporated into the diagnostic assessment of light-chain monoclonal gammopathy of undetermined significance and risk stratification of monoclonal gammopathies.Its usefulness rests on an assumption that deserves closer scrutiny: that a ratio falling outside the conventional diagnostic interval of 0.26-1.65 signifies clonality.This review examines the literature published between June 2016 and June 2026 on the frequency of abnormal κ/λ ratios in individuals without clonal plasma cell disease and the factors that contribute to these findings.The frequency of an abnormal ratio varies substantially according to the population studied, renal function, and the reference interval applied.Use of age-stratified, estimated glomerular filtration rate-banded, or locally derived reference intervals generally reduces the proportion of individuals classified as having an abnormal ratio.Important determinants include reduced glomerular filtration, assay-platform and calibrator variation, advancing age, and polyclonal immune activation associated with autoimmune disease, infection, and critical illness.Elevated concentrations of polyclonal free light chains may also have prognostic associations, while an isolated abnormal ratio may not be reproducible over time.Interpretation of the κ/λ ratio should therefore consider age, renal function, assay characteristics, and the clinical context, with orthogonal laboratory assessment used when appropriate before assigning a plasma cell precursor diagnosis.