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. 2022 May 7;12(5):677.
doi: 10.3390/biom12050677.

Inter-Laboratory Concordance of Cerebrospinal Fluid and Serum Kappa Free Light Chain Measurements

Patrizia Natali  1 , Roberta Bedin  2 , Gaetano Bernardi  3 , Elena Corsini  3 , Eleonora Cocco  4 , Lucia Schirru  4 , Ilaria Crespi  5 , Marta Lamonaca  5 , Arianna Sala  6 , Cinzia Nicolò  7 , Massimiliano Di Filippo  8 , Alfredo Villa  9 , Viviana Nociti  10 , Teresa De Michele  11 , Paola Cavalla  12 , Paola Caropreso  13 , Francesca Vitetta  14 , Maria Rosaria Cucinelli  1 , Matteo Gastaldi  15 , Tommaso Trenti  1 , Patrizia Sola  14 , Diana Ferraro  2   14 , On Behalf Of Rirems Rising Researchers In Ms
Affiliations

Inter-Laboratory Concordance of Cerebrospinal Fluid and Serum Kappa Free Light Chain Measurements

Patrizia Natali et al. Biomolecules. .

Abstract

The kappa index (K-Index), calculated by dividing the cerebrospinal fluid (CSF)/serum kappa free light chain (KFLC) ratio by the CSF/serum albumin ratio, is gaining increasing interest as a marker of intrathecal immunoglobulin synthesis. However, data on inter-laboratory agreement of these measures is lacking. The aim was to assess the concordance of CSF and serum KFLC measurements, and of K-index values, across different laboratories. KFLC and albumin of 15 paired CSF and serum samples were analyzed by eight participating laboratories. Four centers used Binding Site instruments and assays (B), three used Siemens instruments and assays (S), and one center used a Siemens instrument with a Binding Site assay (mixed). Absolute individual agreement was calculated using a two-way mixed effects intraclass correlation coefficient (ICC). Cohen's kappa coefficient (k) was used to measure agreement on positive (≥5.8) K-index values. There was an excellent agreement in CSF KFLC measurements across all laboratories (ICC (95% confidence interval): 0.93 (0.87-0.97)) and of serum KFLC across B and S laboratories (ICC: 0.91 (0.73-0.97)), while ICC decreased (to 0.81 (0.53-0.93)) when including the mixed laboratory in the analysis. Concordance for a positive K-Index was substantial across all laboratories (k = 0.77) and within S laboratories (k = 0.71), and very good (k = 0.89) within B laboratories, meaning that patients rarely get discordant results on K-index positivity notwithstanding the testing in different laboratories and the use of different platforms/assays.

Keywords: cerebrospinal fluid; free light chains; kappa index; multiple sclerosis.

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Conflict of interest statement

Disclosure: D.F., has received travel funding and speaker honoraria from The Binding Site Group (Birmingham, UK) and support to her institution through the supply of Freelite kits for research purposes. P.N., R.B., G.B., E.C. (Elena Corsini), E.C. (Eleonora Cocco), G.C., I.C., M.L., A.S., C.N., V.N., T.D.M., P.C. (Paola Cavalla), P.C. (Paola Caropreso), M.D.F, A.V., F.V., M.G., M.R.C., T.T. and P.S. have nothing to disclose in relation to the study.

Figures

Figure 1
Figure 1
Box-plots showing median (±IQR) CSF (a) and serum (b) KFLC concentrations (mg/L), and K-index (CSF KFLC/Serum KFLC)/(CSF Albumin/serum Albumin) values (c) of the 15 samples across laboratories using Binding Site instruments and assays (B), Siemens instruments and assays (S) or a Siemens instrument coupled with a Binding Site assay (mixed). Upper whiskers show the upper adjacent value (UAV) (largest observation ≤ (third quartile + 1.5 × IQR)); lower whiskers show the lower adjacent value (LAV) (smallest value ≥ (lower quartile − 1.5 × IQR)); black dots show outliers (greater than the UAV or lower than the LAV).
Figure 2
Figure 2
Lin’s concordance correlation coefficient for CSF KFLC measurements in the least concordant (a) pair of laboratories (0.769 (95%CI: 0.666–0.873)) and in the best concordant pair (b) (0.997 (95%CI: 0.994–0.999)).
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