8.6.6. Diagnostic performance in AL amyloidosis

Chapter 8

The largest study that has compared the performance of N Latex FLC and Freelite assays in AL amyloidosis was published by Palladini et al. [945]. This included 426 patients with newly-diagnosed AL amyloidosis from two specialist centres (Pavia, n=353; and Limoges, n=73). When the median λ sFLC concentrations in λ patients were compared, similar values were obtained with Freelite and N Latex FLC assays (197 mg/L vs. 187 mg/L). However, for κ patients, κ sFLC values were significantly higher using Freelite (378 vs. 244 mg/L, p=0.038); this difference was most pronounced at high κ sFLC concentrations. Overall, the diagnostic sensitivity of Freelite (82%) and N Latex FLC (84%) assays was similar, and both improved to 98% in combination with serum and urine immunofixation. Similar results were reported by Mollee et al. [211].

Mahmood et al. [924] confirmed that absolute values reported by Freelite and N Latex FLC assays do not always compare well in AL amyloidosis. In this study, the agreement between κ sFLC results at presentation (n=90) was better than that of λ (κ sFLC R2 = 0.91; λ sFLC R2 = 0.52), as discussed above (Section 8.5.3.). κ/λ sFLC ratios were also discordant between the two assays: 10/90 patients were abnormal by Freelite but normal by N Latex, and 11/90 abnormal by N Latex but normal by Freelite. Similar results were reported by Mollee et al. [211], but the reason for these differences is not understood. A subsequent publication by the same author discussed the difficulties associated with raising monoclonal antibodies to recognise all λ light chain types in AL amyloidosis [993]. This study compared the performance of the Seralite ELISA with N Latex FLC and Freelite assays. All AL amyloidosis patients with monoclonal κ FLCs had an abnormal ratio by all three assays, but for λ patients, the diagnostic sensitivity was much lower for the Seralite ELISA than N Latex or FLC assays (58% vs. 70% and 79%). The authors conclude that the monoclonal antibody-based ELISA assay appears to react poorly with λ sFLCs and is not suitable for diagnosis or monitoring of AL amyloidosis. They also describe how attempts to modify the Seralite ELISA assay to improve λ reactivity failed to improve results. Unsurprisingly, the Seralite ELISA is no longer commercially available.