Abstract
Background: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID). Methods: We enrolled patients who underwent a diagnostic spinal tap throughout two years. KFLC levels were determined using a Freelite assay (Binding Site) and the turbidimetric Optilite analyzer. Results: Of 540 included patients, 223 had a CNSID, and 84 had MS. The kappa index was more sensitive (0.89 versus 0.85) and less specific (0.84 versus 0.89), with the same AUC (0.87) as OCB for MS diagnosis (optimal cut-off: 6.2). Adding patients with a single CSF IgG band to the OCB-positive group slightly increased the AUC (0.88). Likewise, the kappa index (cut-off: 3.9) was more sensitive (0.67 versus 0.50) and less specific (0.81 versus 0.97), with the same AUC (0.74) as OCB, for a CNSID diagnosis. Conclusion: The kappa index and CSF OCB have comparable diagnostic accuracies for a MS or CNSID diagnosis and supply the clinician with useful, complementary information.
Highlights
The detection of cerebrospinal fluid (CSF)-restricted oligoclonal IgG bands (OCB) through isoelectric focusing (IEF) is the current gold standard for determining the presence of intrathecal IgG synthesis
A Multiple Sclerosis (MS) diagnosis is possible in the presence of dissemination in space (DIS) and time (DIT) of demyelinating lesions detected with the brain magnetic resonance imaging (MRI), and in the absence of a “better explanation”: Following the latest revisions to the McDonald’s diagnostic criteria [2], the detection of OCB has gained particular importance since it can substitute for the DIT criterion and permits a MS diagnosis in a greater proportion of patients already at onset [3]
Of 623 patients who had been subjected to a spinal tap for IEF and Cerebrospinal fluid (CSF) kappa free light chains (KFLC) measurements during everyday clinical practice in the Neurology Unit of the Azienda Ospedaliero-Universitaria of Modena (Italy) between January 2018 and January 2020, it was possible to formulate a final diagnosis in 540 cases
Summary
The detection of cerebrospinal fluid (CSF)-restricted oligoclonal IgG bands (OCB) through isoelectric focusing (IEF) is the current gold standard for determining the presence of intrathecal IgG synthesis. Intrathecal immunoglobulin synthesis occurs following activation of the humoral immune response within the intrathecal compartment and may be present in a number of different infectious or inflammatory central nervous system (CNS) disorders, including Multiple Sclerosis (MS) [1]. Light chains are produced in excess of Ig [4], and the intrathecal synthesis of free light chains (FLC), and in particular of kappa FLC (KFLC) is gaining increasing interest as a possibly more sensitive, less costly and less time-consuming, quantitative marker of intrathecal immunoglobulin synthesis compared to OCB detection. Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID). The kappa index was more sensitive (0.89 versus 0.85) and less specific (0.84 versus 0.89), with the same AUC (0.87) as OCB for MS diagnosis (optimal cut-off: 6.2)
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