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Recent studies have found that patients with MS frequently exhibit intrathecal production of kappa free light chains (KFLC), serving as a potential alternative or adjunct measure to oligoclonal bands. Because measuring the cerebrospinal fluid KFLC index has several technical advantages over measuring oligoclonal bands, comparing the diagnostic utility of the KFLC index and oligoclonal bands has clinical utility, particularly in resource-poor areas. This study compared the diagnostic accuracy of the KFLC index with that of oligoclonal bands in predicting subsequent relapse or meeting MRI definitions of dissemination in space and time in a population of patients presenting with clinically isolated syndrome. There was a high concordance between the KFLC index and oligoclonal bands, with the KFLC index performing slightly better than oligoclonal bands in terms of diagnostic accuracy.
These findings suggest that the KFLC index represents an alternative to oligoclonal bands as a marker of intrathecal antibody production in MS and that it might also have a slightly greater diagnostic accuracy than oligoclonal bands. Given the technical advantages of measuring the KFLC index, it might have a role as an alternative criterion for an MS diagnosis.
Intrathecal production of kappa free light chains (KFLC) occurs in multiple sclerosis and can be measured using the KFLC index. KFLC index values can be determined more easily than oligoclonal bands (OB) detection and seem more sensitive than the immunoglobulin (Ig)G index to diagnose multiple sclerosis. We assessed the value of OB, KFLC index cut-offs 5.9, 6.6, and 10.61, and IgG index to diagnose multiple sclerosis with prospectively acquired data from a clinically isolated syndrome (CIS) inception cohort. We selected patients with sufficient data to determine OB positivity, MRI dissemination in space (DIS) and time (DIT), IgG index, and sufficient quantities of paired CSF and blood samples to determine KFLC indexes (n = 214). We used Kendall´s Tau coefficient to estimate concordance; calculated the number of additional diagnoses when adding each positive index to DIS and positive OB; performed survival analyses for OB and each index with the outcomes second attack and 2017 MRI DIS and DIT; and estimated the diagnostic properties of OB and the different indexes for the abovementioned outcomes at five years. OB were positive in 138 patients (64.5%), KFLC-5.9 in 136 (63.6%), KFLC-6.6 in 135 (63.1%), KFLC-10.61 in 126 (58.9%) and IgG index in 101 (47.2%). The highest concordance was between OB and KFLC-6.6 (τ=0.727) followed by OB and KFLC-5.9 (τ=0.716). Combining DIS plus OB or KFLC-5.9 increased the number of diagnosed patients by 11 (5.1%), with KFLC-6.6 by 10 (4.7%), with KFLC-10.61 by 9 (4.2%), and with IgG index by 3 (1.4%). Patients with positive OB or indexes reached second attack and MRI DIS and DIT faster than patients with negative results (P < 0.0001 except IgG index in second attack: P = 0.016). In multivariable Cox models [aHR (95% CI)], the risk for second attack was very similar between KFLC-5.9 [2.0 (0.9-4.3), P = 0.068] and KFLC-6.6 [2.1 (1.1-4.2), P = 0.035]. The highest risk for MRI DIS and DIT was demonstrated with KFLC-5.9 [4.9 (2.5-9.6), P < 0.0001], followed by KFLC-6.6 [3.4 (1.9-6.3), P < 0.0001]. KFLC-5.9 and KFLC-6.6 had a slightly higher diagnostic accuracy than OB for second attack (70.5, 71.1, and 67.8) and MRI DIS and DIT (85.7, 85.1, and 81.0). KFLC indexes 5.9 and 6.6 performed slightly better than OB to assess multiple sclerosis risk and in terms of diagnostic accuracy. Given the concordance between OB and these indexes, we suggest using DIS plus positive OB or positive KFLC index as a modified criterion to diagnose multiple sclerosis.
The kappa free light chain index and oligoclonal bands have a similar role in the McDonald criteria
Brain 2022 Jun 21;[EPub Ahead of Print], G Arrambide, C Espejo, P Carbonell-Mirabent, R Dieli-Crimi, M Rodríguez-Barranco, M Castillo, C Auger, S Cárdenas-Robledo, J Castilló, Á Cobo-Calvo, I Galán, L Midaglia, C Nos, S Otero-Romero, J Río, B Rodríguez-Acevedo, M Ruiz-Ortiz, A Salerno, P Tagliani, C Tur, A Vidal-Jordana, A Zabalza, J Sastre-Garriga, A Rovira, M Comabella, M Hernández-González, X Montalban, M Tintore