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Cerebrospinal fluid kappa-free light chains for MS diagnosis

Presented by
Dr Harald Hegen, Medical University of Innsbruck, Austria

A systematic review and meta-analysis indicated that the kappa-free light chains (κ-FLC) index has a similar diagnostic accuracy in MS as oligoclonal bands (OCB). Intrathecal κ-FLC synthesis might be included into the next revision of MS diagnostic criteria as an additional tool to measure intrathecal immunoglobulin synthesis.

Intrathecal IgG synthesis is a hallmark of MS [1]. Determination of the OCB in cerebrospinal fluid (CSF) is the gold standard for detecting this. A highly-promising alternative method for the assessment of intrathecal inflammation is the quantification of κ-FLC in CSF. In the context of a consensus statement on how to best to evaluate CSF in patients suspected of MS, a systematic review and meta-analysis were performed by Dr Harald Hegen (Medical University of Innsbruck, Austria) and colleagues to compare the diagnostic value of κ-FLC and OCB [2,3].

Included were 34 studies that assessed diagnostic sensitivity and specificity of both methods to discriminate patients with MS or a clinically isolated syndrome (CIS) from control participants. The diagnostic sensitivity and specificity of κ-FLC were almost identical to those of OCB, confirming the diagnostic performance of κ-FLC (see Table). A central issue here is a cut-off value for the κ-FLC index, which was determined at 7.0.

Table: Performance of CSF evaluation using κ-FLC or OCB [2]

k-FLC, kappa-free light chains; OCB, oligoclonal bands.

An international expert panel reached consensus on several recommendations for standard CSF evaluation. One of these recommendations was that determination of intrathecal κ-FLC synthesis, e.g. by the κ-FLC index, should be included in the next revision of MS diagnostic criteria. The panel's conclusions were endorsed by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

  1. Bonnan M. Mult Scler Int. 2015;2015:296184.
  2. Hegen H, et al. Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: a systematic review, meta-analysis and consensus statement. Abstract O056, ECTRIMS 2022, 26–28 October, Amsterdam, the Netherlands.
  3. Hegen H, et al. Wien Med Wochenschr. 2022;172(15-16):337–345.

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