Received on March 12, 2004
Accepted on June 28, 2004

Clinical Immunology

Kappa Free Light Chains in Cerebrospinal Fluid as Markers of Intrathecal Immunoglobulin Synthesis

¹ Institute of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg University, Mainz, Germany
² Department of Neurology, Johannes Gutenberg University, Mainz, Germany

^* To whom correspondence should be addressed. E-mail: lackner{at}zentrallabor.klinik.uni-mainz.de.

Background: Intrathecal immunoglobulin synthesis is observed in several inflammatory disorders of the central nervous system, but its detection by current laboratory tests is either tedious or relatively insensitive. We assessed the diagnostic accuracy of an assay for free light chains (FLC) in cerebrospinal fluid (CSF) and serum, and compared it with traditional tests for intrathecal immunoglobulin synthesis.

Methods: FLCs were measured by nephelometry in CSF/serum pairs from 112 patients. Samples were excluded if artificial blood contamination of CSF (n = 12) or monoclonal bands in both CSF and serum (n = 5) were present. The remaining sample pairs were grouped according to the presence (n = 71) or absence (n = 24) of oligoclonal bands. Data were analyzed as FLC concentrations in CSF, as FLC CSF/serum ratios, and by use of the quotient diagram described previously for immunoglobulins.

Results: Both FLC concentrations in CSF and the FLC CSF/serum ratio identified patients with oligoclonal bands with high specificity and sensitivity. The areas under the ROC curves were 0.991 (95% confidence interval, 0.944-0.998) and 0.978 (0.924-0.996), respectively. Exclusion of patients with impaired blood-CSF barrier function further improved diagnostic accuracy. To account for patients with impaired blood-CSF barrier function, data were also analyzed in a quotient diagram. Only two patients without detectable oligoclonal bands would have been misclassified by this approach.

Conclusions: Our data indicate that the nephelometric assay for FLCs in CSF reliably detects intrathecal immunoglobulin synthesis. This automated and quantitative method could simplify the diagnostic procedure for CSF analysis in the routine laboratory.