High levels of cerebrospinal fluid free kappa chains predict conversion to multiple sclerosis

Background: A clinically isolated syndrome (CIS) may be the initial presentation of multiple sclerosis (MS). However, some CIS never develop MS. The identification of patients at risk of MS conversion is crucial as early treatment may improve their outcome. Free kappa chains (FKC) are increased in cerebrospinal fluid (CSF) of MS patients. We studied the accuracy of CSF FKC level measurement, using a new nephelometric test, to predict conversion of CIS patients to MS. Methods: We calculated linearity and inter-assay variability of the FKC test for CSF values and quantified this protein in CSF from 25 patients with non-inflammatory neurological diseases (NIND) and 78 consecutive CIS patients. We assessed whether high CSF FKC levels associate with CIS conversion to clinically definite MS, defined as the onset of new relapses during follow-up. Results: Between 0.1 and 5 mg/l the FKC test showed linearity of 0.98 and inter-assay correlation coefficient of = 0.99. A cut-off value of 0.53 mg/l (mean + 2SD of NIND group CSF FKC values) was calculated. CIS patients with CSF FKC above this value showed earlier conversion to MS in univariate and multivariate Cox analysis (HR = 6.41: 95% CI = 1.88-21.78, p = 0.003). Conclusion: High CSF FKC levels accurately predict CIS patient conversion to MS. (C) 2012 Elsevier B.V. All rights reserved.