DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF INTRATHECAL SYNTHESIS OF IMMUNOGLOBULIN FREE LIGHT CHAINS IN MULTIPLE SCLEROSIS

Abstract

Background: Increased intrathecal synthesis of immunoglobulins and oligoclonal synthesis (OCB) are among the major immunological findings in MS. Free light chains (FLC) are fragments of immunoglobulin molecules that are produced in parallel to OCB and their production reflects total immunoglobulin synthesis within CNS. Elevated concentration of the free light chains kappa (K-FLC) and lambda (L-FLC) can be found in CSF but its diagnostic and prognostic significance has to be determined. Objectives: We evaluated parameters of intrathecal K-FLC and L-FLC production as an additional diagnostic and prognostic biomarker in MS. Methods: Concentrations of albumin was measured with turbidimetric method, K-FLC and L-FLC were detected with novel ELISA based on a pair of monoclonal antibodies, and OCB with isoelectric focusing were studied in pared CSF and serum samples of 151 patients, including 92 patients with MS, 33 CIS patients followed until CDMS diagnosis and 26 patients with other inflammatory neurologic diseases of CNS. Several quotients and indices (Qalb, FLC quotient (Q) and indices (I) and kappa/lambda ratio (K/L ratio)) were calculated to deduce better diagnostic tool. Results: Concentration of K-FLC, Q-kappa(Q-K), Index Kappa(I-K) were significantly elevated (p< 0.0001) in MS and CIS-MS group as compared with control group. K/L ratio was significantly elevated only in MS group. Concentration of K-FLC and related indices (Q-K, I-K) were significantly higher in OCB-positive samples than in OCB-negative (p< 0,01). ROC analysis has shown that among all diagnostic biomarkers Q-K is the best for MS diagnosis. The usefulness of Q-K can also be confirmed by positive Q-K in OCB-negative group in 42% of MS cases. Also L-FLC negatively correlated with time of CIS conversion to MS (r=-0.5763, p=0.0026). Conclusions: Immunoglobulin FLC were found to be promising diagnostic and prognostic marker in MS.