New rapid urine test for the identification and quantitation of immunoglobulin free light chains (Bence Jones Proteins)

Background. Monoclonal κ and λ immunoglobulin free light chains (FLC) in the urine are important biomarkers for the diagnosis and monitoring of a number of plasma cell dyscrasias including multiple myeloma. To date, laboratory FLC tests provide the only means of quantitating FLC and often have a slow turnaround time that prevents early diagnosis or prompt identification of changes in disease activity. Furthermore, the gold standards for identifying (immunofixation electrophoresis; IFE) and quantitating (densitometry) FLC in the urine have a number of limitations. IFE lacks analytical sensitivity (LOD >10-20 mg/L) and interpretation is often subjective. Densitometry has high inter-test variability that contributes to an inter-lab CV% of 50- 95% in the UK National External Quality Assessment Service (NEQAS), and is poorly sensitive meaning that urines need to be concentrated before measurement, sometimes up to 150-fold. Further, clinical manifestations such as proteinuria may obscure monoclonal FLC bands and makes identification and quantitation of monoclonal protein bands inaccurate. Therefore, we have developed a rapid test (Seralite®) that identifies abnormal FLC levels in unconcentrated urine or blood in 10 minutes. Seralite® quantitates κ and λ FLC levels simultaneously using highly specific anti-κ and anti-λ FLC monoclonal antibodies. Methods: Seralite® validation was conducted by retrospective analysis of urine from patients presenting with multiple myeloma (n=100). All samples were also measured for FLC by electrophoresis immunofixation; densitometry on concentrated urines; and a recently validated new Luminex assay that incorporates the same mAbs as Seralite®. Results: Seralite® displayed excellent clinical concordance with Luminex. Analysis of IFE results revealed that Seralite® had no false negatives, and correlated excellently with densitometry. Conclusion: Seralite® detected all FLC in urine from 100 myeloma patients at diagnosis. Prospective use of Seralite® to diagnose and monitor plasma cell dyscrasias including multiple myeloma should now be investigated. The utility of Seralite® in the context of other FLC related disorders including AL amyloidosis should also be established.