Evaluation of a new ELISA assay for monoclonal free‐light chain detection in patients with cardiac amyloidosis

Abstract The causal protein of amyloid light‐chain (AL) amyloidosis is a monoclonal immunoglobulin free light chain (mFLC), which must be quantified in the serum for patient diagnosis and monitoring. Several manufacturers commercialize immunoassays that quantify total kappa (κ) and lambda (λ) FLC, but results can differ greatly between these tests. Here, we compared a recently developed enzyme‐linked immunosorbent assay (ELISA) (Sebia) with N‐Latex immunonephelometry (Siemens) in 96 patients diagnosed with AL amyloidosis (histologically confirmed) and 48 non‐AL patients sent to our referral center for suspicion of cardiac amyloidosis. ELISA free‐light chain difference (dFLC) were lower than N‐Latex values, and agreement between methods was reduced in the case of involved λ FLC. Diagnosis sensitivity and specificity were >85% with both assays. A receiver operating characteristic analysis indicated that ELISA performances could be improved by using a higher value for the lower limit of the κ/λ ratio. We also assessed Freelite (The Binding Site) in a subgroup of these same AL patients, including 18 cases with normal κ/λ ratio by at least one assay. Only two patients had normal κ/λ ratio with all three assays. Overall, ELISA demonstrated slightly lower sensitivity than N‐Latex but may be an alternative to nephelometry/turbidimetry in certain difficult cases.