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Oral Sessions
Day 2, June 23（Mon.） 12:10-12:25
Room C (Top of Yaima)
- 2C-O1-1210
Determination of Clonality of Monoclonal Serum Free Light Chains by On-Probe Extraction Coupled with Liquid Chromatography-Mass Spectrometry
(1Stanford Univ, 2Stanford Health Care)
Priscilla Yeung1,2, Yajing Liu1, Ashley Ruan1, Christina Kerr1, Run-Zheng Shi1,2, David Iberri1, oRuben Luo1,2
Introduction
Multiple myeloma (MM) is the second most common hematolymphoid malignancy. An essential clinical marker of MM is monoclonal serum free light chain (FLC), which refers to a circulating monoclonal antibody light chain that is unbound to heavy chain. The widely used immunoassay quantifies total serum FLCs, including the polyclonal background. Although a skewed kappa-to-lambda ratio of FLCs is used as a proxy for clonality, some patients, such as those with renal diseases, can have both kappa and lambda FLCs elevated, resulting in ambiguity in clinical diagnosis. The purpose of this study was to develop an assay that couples on-probe extraction with mass spectrometry (OPEX-MS) to determine the clonality of serum FLCs.
Methods
Immunocapture with on-probe extraction (OPEX) was performed using biolayer interferometry (BLI) probes and capture antibodies on a BLI analyzer. Captured FLCs were eluted using 0.3% formic acid. Mass spectrometry analysis was performed with an Orbitrap LC-MS system.
Results
Four cohorts of samples were analyzed based on immunoassay results: Negative (n = 50), Kappa Positive (n = 49), Lambda Positive (n = 46), and Dual Elevated (n = 100). OPEX-MS identified monoclonal FLCs in a small subset of the Dual Elevated cohort with a normal kappa-to-lambda ratio, demonstrating that the immunoassay was ineffective in the detection of monoclonal FLC for this type of samples.
Novel Aspect
OPEX-MS is an innovative solution to determine clonality in patients with difficult-to-interpret FLC immunoassay results.