Free light chains kappa can differentiate between myelitis and noninflammatory myelopathy

Abstract

ObjectiveTo 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.MethodsThis 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.ResultsNinety-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%ConclusionsWith 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.

The Increasing Role of Kappa Free Light Chains in the Diagnosis of Multiple Sclerosis

“…Studies included in this review used immunofixation, immunoblotting, or Western blotting assays for OCB determination. These studies reached a diagnostic sensitivity between 78 and 98% when OCB positivity was not an inclusion criterion [4,[18][19][20][21][22][23]25,26,28,29,33,. Thus, in the majority of these studies, KFLC measurement was superior to OCB determination [4,[18][19][20][21][22][23]25,26,28,29,33,.…”

“…These studies reached a diagnostic sensitivity between 78 and 98% when OCB positivity was not an inclusion criterion [4,[18][19][20][21][22][23]25,26,28,29,33,. Thus, in the majority of these studies, KFLC measurement was superior to OCB determination [4,[18][19][20][21][22][23]25,26,28,29,33,. To date, there is no comparative study investigating which OCB method is the most sensitive.…”

“…In a cohort consisting of 100 MS patients, 24 CIS patients with conversion to MS and 44 CIS patients without conversion to MS, the diagnostic superiority of Reiber's diagram for KFLC was shown [24]. Reiber's diagram was applied in further studies and a diagnostic sensitivity of 97% (94%, 99%) and specificity of 75% (53%, 97%) was reported [24][25][26][27][28][29]43,68,75]. Further, Süße et al used Reiber's diagram to determine a cut-off value based on the intrathecal fraction of KFLC (KFLC IF according to Reiber's diagram) in order to differentiate between neuromyelitis optica spectrum disorders (NMOSD) and MS [25,26].…”

“…Reiber's diagram was applied in further studies and a diagnostic sensitivity of 97% (94%, 99%) and specificity of 75% (53%, 97%) was reported [24][25][26][27][28][29]43,68,75]. Further, Süße et al used Reiber's diagram to determine a cut-off value based on the intrathecal fraction of KFLC (KFLC IF according to Reiber's diagram) in order to differentiate between neuromyelitis optica spectrum disorders (NMOSD) and MS [25,26]. Summarizing, the authors recommend the application of Reiber's diagram for KFLC for the interpretation of KFLC concentrations.…”

“…In 2019, Reiber and colleagues developed a quotient diagram based on a hyperbolic function to establish a reference range for KFLC in CSF similar to the hyperbolic function for the immunoglobulins A, G, and M [25]. This reference range has already been successfully applied in different studies and showed a superior performance in terms of diagnostic sensitivity for the detection of intrathecal inflammation as compared with other reference values for KFLC and the gold standard OCB [24][25][26][27][28][29]. However, the role of KFLC in other neurologic diseases than MS is not entirely clear.…”