Free light chains kappa can differentiate between myelitis and noninflammatory myelopathy

Abstract

Objective: To test the hypothesis that the intrathecal synthesis of free light chain kappa (FLC-k) can be used as a CSF biomarker to differentiate patients with myelitis due to multiple sclerosis (MS), myelitis due to neuromyelitis optica spectrum disease (NMOSD), and noninflammatory myelopathy, we analyzed FLC-k in 26 patients with MS myelitis, 9 patients with NMOSD myelitis, and 14 patients with myelopathy.

Methods: This is a retrospective monocentric cohort study. FLC-k were analyzed using the nephelometric Siemens FLC-k kit in paired samples of CSF and sera. Intrathecal fraction (IF) of FLC-k was plotted in a FLC-k quotient diagram.

Results: Ninety-six percent of patients with MS myelitis had an intrathecal synthesis of FLC-k in comparison with 55.6% for NMOSD and 14.3% of patients with noninflammatory myelopathy. The locally synthesized absolute amount of FLC-k was significantly higher in patients with myelitis due to MS than in patients with NMOSD (p = 0.038) or noninflammatory myelopathy (p < 0.0001). The sensitivity of FLC-k synthesis to detect inflammation in patients with myelitis is 85.7%. Using a receiver operating characteristic analysis, FLC-k IF >78% can discriminate patients with myelitis due to MS and NMOSD with a sensitivity of 88.5% and a specificity of 88.9% CONCLUSIONS: With the hyperbolic reference range in quotient diagrams for FLC-k, it is possible to distinguish inflammatory myelitis from noninflammatory myelopathies. An FLC-k IF >78% can be a hint to suspect myelitis due to MS rather than NMOSD.

Figure 1. Data of the cohort in a double logarithmic FLC-k Reibergram and ROC analysis

(A) Data of the FLC-k quotients in a double logarithmic FLC-k Reibergram. The black line shows Q_FLC-k(lim); the red line shows the Q_FLC-k(mean). The green line is the lower limit of the reference range Q_FLC-k(low). Ninety-six percent of the FLC-k quotients in patients with myelitis due to MS or CIS are above the upper discrimination line Q_lim. Fifty-five of the patients with a myelitis due to NMOSD showed FLC-k quotients > Q_lim. Approximately 85.7% of patients with a noninflammatory myelopathy had FLC-k values < Q_lim. (B) ROC analysis in respect to FLC-IF > Q_lim. The AUC is 0.915. With a cut-off of 78.6% IF, sensitivity is 88.5%, specificity 88.9% to discriminate patients with MS/CIS and NMOSD. Box plots: The locally synthesized absolute amount of FLC-k (K_loc = [Q_kappa(total) − Q_kappa(mean)] × S_kappa [mg/L]) is significantly higher in patients with myelitis due to MS than in patients with NMOSD (p = 0.038). AUC = area under the curve; CIS = clinically isolated syndrome; FLC-k = free light chains kappa; IF = intrathecal fraction; NMOSD = neuromyelitis optica spectrum disease; OCB = oligoclonal band; Q = quotient; ROC = receiver operating characteristic.

Figure 2. Data of FLC-k quotients of a patient with NMOSD in a double logarithmic FLC-k Reibergram

See also the legend of figure 1. Inverted triangle: CSF analysis 07/2008 before immunotherapy, IF 95.1%; triangle: CSF analysis 02/2013 12 months after autologous-SCT, IF 12.5%; square: CSF analysis 06/2013, IF 34.5%; rectangle CSF analysis 02/2017, IF 77.8; circle CSF analysis 02/2017 IF 88.3% (new disease activity). FLC-k = free light chains kappa; IF = intrathecal fraction; neg = negative; NMOSD = neuromyelitis optica spectrum disease; OCB = oligoclonal band; pos = positive; Q = quotient; SCT = stem cell transplantation.