The association of intrathecal production of immunoglobulin free light chains and progression of multiple sclerosis

Abstract

Concentrations of kappa FLC can help to define the prognosis of MS early at the disease course. Although low concentrations of FLC do not exclude a severe disease phenotype, patients with high K-FLC concentrations are at greater risk for faster MS progression, probably, due to impaired reparation of neural tissue. Measurement of FLC concentrations can be used to determine a therapeutic tactics in patients with MS.

The Increasing Role of Kappa Free Light Chains in the Diagnosis of Multiple Sclerosis

“…To further investigate the role of KFLC as a prognostic biomarker in CIS patients, studies with longer follow-up duration are needed. The mean follow-up time of the studies included in this review was only 35 months (min-max: 24-58 months) [43,50,53,55,58,61,68,69,73,[82][83][84]86,87,130]. Furthermore, the knowledge about KFLC in other neurologic diseases with intrathecal inflammation is rare.…”

“…In contrast, other studies denied a correlation between disease progression evaluated by EDSS and KFLC CSF concentration or KFLC indices [43,66,69,77,84,87]. In some studies, high KFLC CSF concentrations or KFLC indices were associated with a higher risk for CIS patients to be later diagnosed with definite MS [43,50,53,54,61,68,69,73,82,83,86,130]. In other studies, this correlation could not have been observed, and CIS patients with conversion to MS did not reveal elevated CSF KFLC [55,84,87].…”

“…Some studies, which investigated the utility of FLC measurement in the diagnosis of MS, empirically created cut-off values either for the absolute KFLC or LFLC concentrations in CSF, CSF/serum KFLC, and LFLC quotients (Q KFLC , Q LFLC ), CSF KFLC/IgG, and LFLC/IgG ratios or KFLC/LFLC concentration ratios to determine KFLC or LFLC positivity [4,19,20,23,33,47,48,50,[52][53][54][55][60][61][62][63][64][65][66][67][68]73,74,76,77,85,[88][89][90][91]130]. The cut-off for the CSF KFLC concentration varied between 0.103 µg/mL and 7 mg/L and a mean diagnostic sensitivity and specificity of 86% (95% confidence interval (80%, 92%)) and 91% (86%, 96%) was reached while the threshold for CSF LFLC concentration varied between 0.0175 µg/mL and 4.3 mg/L and a mean sensitivity and specificity of 67% (48%, 85%) and 82% (67%, 96%) was reported [4,19,20,23,33,47,48,50,[52][53][54][55][60]…”

“…Similarly, the prediction of disease and disability progression based on KFLC concentrations was evaluated heterogeneously. Some studies revealed a significant correlation between high KFLC concentrations in CSF and early disability or disability progression mostly estimated by the EDSS [61,67,72,76,81,98,130]. In contrast, Rathbone and colleagues observed that a high CSF KFLC/LFLC ratio was associated with a lower median EDSS [52].…”

High Levels of Cerebrospinal Fluid Kappa Free Light Chains Relate to IgM Intrathecal Synthesis and Might Have Prognostic Implications in Relapsing Multiple Sclerosis

“…Similarly, an excess of KFLC-index has been associated with a higher probability of CIS conversion to MS (9), and patients with KFLC-index >100 at baseline had twice as high a probability of a second clinical attack within 12 months (27). Patients with higher baseline values of KFLC achieved EDSSconfirmed progression in shorter periods and showed a significant positive correlation with disability at follow-up, independently of the effects of age, OCB status at baseline, and DMT exposure (18,(28)(29)(30). Our conclusions should be interpreted cautiously due to study limitations such as low sample size, the low incidence in prognostic endpoints, and higher incidence of OCMBs as compared to other studies that might have introduced potential sources of bias.…”