Abstract

In this retrospective, monocentric cohort study, we tested if an intrathecal free light chain kappa (FLC-k) synthesis reflects not only an IgG but also IgA and IgM synthesis. We also analysed if FLC-k can help to distinguish between an inflammatory process and a blood contamination of cerebrospinal fluid (CSF). A total of 296 patient samples were identified and acquired from patients of the department of Neurology, University Medicine Greifswald (Germany). FLC-k were analysed in paired CSF and serum samples using the Siemens FLC-k kit. To determine an intrathecal FLC-k and immunoglobulin (Ig) A/-M-synthesis we analysed CSF/serum quotients in quotient diagrams, according to Reiber et al. Patient samples were grouped into three cohorts: cohort I (n = 41), intrathecal IgA and/or IgM synthesis; cohort II (n = 16), artificial blood contamination; and the control group (n = 239), no intrathecal immunoglobulin synthesis. None of the samples had intrathecal IgG synthesis, as evaluated with quotient diagrams or oligoclonal band analysis. In cohort I, 98% of patient samples presented an intrathecal synthesis of FLC-k. In cohort II, all patients lacked intrathecal FLC-k synthesis. In the control group, 6.5% presented an intrathecal synthesis of FLC-k. The data support the concept that an intrathecal FLC-k synthesis is independent of the antibody class produced. In patients with an artificial intrathecal Ig synthesis due to blood contamination, FLC-k synthesis is lacking. Thus, additional determination of FLC-k in quotient diagrams helps to discriminate an inflammatory process from a blood contamination of CSF.

Highlights

  • One method to distinguish blood derived from intrathecal, synthesized IgG, -A, or -M is the interpretation of IgG, -A, -M cerebrospinal fluid (CSF) and serum quotients (QIgG, QIgA, and QIgM; y-axis) in reference to the albumin CSF, and the serum quotient (Q-alb; x-axis) in relation to the empirically-derived hyperbolic reference range established by Reiber et al [1]

  • Cohort II was comprised of 16 patients with artificial IgM and/or IgA synthesis through blood contamination

  • The control group was comprised of 239 patients with neither intrathecal Ig synthesis nor isolated oligoclonal bands (OCB) in the CSF

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Summary

Introduction

One method to distinguish blood derived from intrathecal, synthesized IgG, -A, or -M is the interpretation of IgG, -A, -M CSF and serum quotients (QIgG, QIgA, and QIgM; y-axis) in reference to the albumin CSF, and the serum quotient (Q-alb; x-axis) in relation to the empirically-derived hyperbolic reference range established by Reiber et al [1]. This concept incorporates the CSF flow rate as the major influence on CSF protein concentration. For the detection of synthesis of intrathecal IgG, but not IgA or -M, the most sensitive method is the analysis of oligoclonal bands (OCB) by isoeletric focusing and immunodetection [2,3]

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