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 to predict conversion of CIS patients to MS.
METHODS: We quantified the FKC 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 5mg/l the FKC test showed linearity of 0.98 and inter-assay correlation coefficient of =0.99. A cut-off value of 0.53mg/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.
Antibodies are made up of a heavy and a light chain. The light chain are made from either lamda or kappa gene variants. There are normally joined to the heavy chains by disulphide bonds where a sulphur on one chain binds to a sulphur on the other chain. However the light chains can occur as free molecules. When people presented with their first neurological sign, those with free light chains had a greater chance of developing MS. Given that their are a increasing number of trials aimed at treating people at the CIS stage this may be an additional test that may indicate the chances of subsequently developing MS.