The kappa free light chain index and oligoclonal bands have a similar role in the McDonald criteria

Abstract

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.

High levels of kappa free light chain synthesis predict cognitive decline in relapsing-remitting multiple sclerosis

“…Furhtermore, KFLC-index has been recently shown to predict or be associated with early inflammatory disease activity (19,22,24), and in the present study we show that high levels are predictive of cognitive decline. We have previously shown that treatment with fingolimod and alemtuzumab did not influence KFLC-index levels (18).…”

“…Kappa free light chain (KFLC) index ([CSF KFLC/serum KFLC]/ [CSF albumin/serum albumin]), a marker for intrathecal production of free kappa chains, has been increasingly recognized in recent years for its diagnostic (16)(17)(18)(19)(20) and prognostic (21)(22)(23)(24)(25) potential in RRMS. Although the association between intrathecal Ig synthesis as determined by IgG-OCBs and CI has been previously studied (26,27), the prognostic role of KFLC synthesis in relation to CI remains unknown.…”

Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis

“…Therefore, adding OCB to KFLC biomarkers may be helpful in atypical cases. Based on our results, the results of other diagnostic studies, [7][8][9][10][11][12][13][14] the ones of predictive studies, 21,23,34 and the knowledge into MS red flags, 1,35,36 we propose an algorithm that integrate KFLC biomarkers to diagnose MS (eFigure 3, links.lww.com/NXI/A753).…”

“…Moreover, predictive studies 23,34 found that KFLC index predict second clinical attack or MRI dissemination in space and time, in patients with CIS, with a good accuracy, slightly better than OCB. 23,34 Because KFLC measurement is an easier way to prove intrathecal B-cell activity, with at least as good diagnostic performances than OCB, KFLC index or KFLC IF could be used in clinical practice instead of OCB as first-line MS biomarker. Nonetheless, using a combination of KFLC and OCB significantly increases specificity for MS diagnosis.…”

“…This result is in line with predictive studies that showed that KFLC could predict MS disability 20 and second clinical attack in patients with CIS. 24,34,41,42…”