Elevated CSF free kappa light chains support the diagnosis of multiple sclerosis

Background: Several studies have demonstrated kappa free light chains (KFLCs) in CSF of MS-patients but so far only small cohorts have been examined and mainly KFLCs were simply qualitatively detected. However, using a recently developed particule immunoassay protocol (FreeliteTM, The Binding Site, UK) it has become possible to make rapid and automated quantitative measurements of KFLCs using nephelometry.

Methods: Between 2001 and 2006 we collected CSF and serum samples from 438 unselected patients including a group of 70 MS-patients (41 definite MS, 29 possible MS). Fluids were analysed using nephelometry and isoelectric focusing. We then retrospectively compared results with the patients diagnoses, MS-diagnostic was performed making use of the diagnostic criteria published by McDonald et al.

Results: Best diagnostic performance was achieved by constructing a KFLC-index compareable to the IgG-index: Concentration of KFLCs in CSF is divided by the concentration of KFLCs in serum; the result is then divided by the albumin quotient. In our study the threshold value for pathologically elevated KFLC-indices was 5,9. Out of the MS-group (n=70) with expected intrathecal IgG synthesis, 67 patients had elevated KFLC-indices, 64 patients showed OCB and 56 patients had elevated IgG-indices (>0,6). This results in a sensitivity of 0,96 for the KFLC-index compared to 0,91 for OCB and 0,80 for the IgG-index. In the CSF of three MS-patients none of these methods could detect an inflammatory process. Other intrathecal inflammations like meningitis/encephalitis (n=41), guillain-barre-syndrome (n=15), neuroborreliosis (n=15) etc. were also often associated with an elevated KFLC-index. Therefore the specificity of KFLC-index ≥5,9 for the MS group (0,86) is lower than that of OCB (0,92) but still distinctly higher compared to the IgG-index (0,77).

Conclusion: In this study an elevated KFLC-index represents the most sensitive and specific quantitative diagnostic parameter for MS. As it is measured by automated, daily available laboratory methods the KFLC-index could supply an important indication of an intrathecal immunological process for patients suspected to suffering from MS before OCB is performed. Moreover an elevated KFLC-index could strengthen the diagnosis of MS-patients with no OCB.