Background: Kappa free light chains (KFLC) in cerebrospinal fluid (CSF) have emerged as quantitative biomarkers of intrathecal humoral immune activity and are now included in diagnostic criteria for multiple sclerosis (MS). The aim of this study was to evaluate the relationship between quantitative and qualitative KFLC parameters and intrathecal immunoglobulin synthesis in MS. Methods: In this retrospective monocentric study, paired CSF and serum samples from 242 neurological patients, 171 with MS, were analyzed. KFLC, IgG and IgM concentrations were measured by turbidimetry and intrathecal synthesis was assessed using established linear and nonlinear indices. IgG and KFLC oligoclonal bands (OCB) were detected by isoelectric focusing followed by immunoblotting. Alternative K-index thresholds were explored and the independent contribution of IgG and IgM intrathecal fractions was assessed using multivariable regression models. Results: K-index positivity showed a strong association with intrathecal IgG synthesis and IgG OCB in MS patients (all p < 0.0001) and was independent of age and sex. Multivariable analysis demonstrated that the K-index was independently associated with IgG (p < 0.0001), but not IgM (p = 0.738) intrathecal synthesis. Qualitative KFLC oligoclonality was frequently observed in patients with IgG OCB (89.19%). Conclusions: KFLC are confirmed as a valuable complementary biomarker to IgG OCB in MS. K-index values should be evaluated in conjunction with clinical features, imaging data, and ongoing or prior treatments, as KFLC levels may be dynamic and treatment sensitive, with a potential risk of misclassification in diagnostically borderline cases.
Beyond oligoclonal bands: the independent role of kappa free light chains in the diagnostic workup of multiple sclerosis
Candeloro, Raffaella
;Laudisi, Michele;Ferri, Caterina;Baldi, Eleonora;Negri, Giovanna;Ghisellini, Sara;Pugliatti, Maura;Castellazzi, Massimiliano
2026
Abstract
Background: Kappa free light chains (KFLC) in cerebrospinal fluid (CSF) have emerged as quantitative biomarkers of intrathecal humoral immune activity and are now included in diagnostic criteria for multiple sclerosis (MS). The aim of this study was to evaluate the relationship between quantitative and qualitative KFLC parameters and intrathecal immunoglobulin synthesis in MS. Methods: In this retrospective monocentric study, paired CSF and serum samples from 242 neurological patients, 171 with MS, were analyzed. KFLC, IgG and IgM concentrations were measured by turbidimetry and intrathecal synthesis was assessed using established linear and nonlinear indices. IgG and KFLC oligoclonal bands (OCB) were detected by isoelectric focusing followed by immunoblotting. Alternative K-index thresholds were explored and the independent contribution of IgG and IgM intrathecal fractions was assessed using multivariable regression models. Results: K-index positivity showed a strong association with intrathecal IgG synthesis and IgG OCB in MS patients (all p < 0.0001) and was independent of age and sex. Multivariable analysis demonstrated that the K-index was independently associated with IgG (p < 0.0001), but not IgM (p = 0.738) intrathecal synthesis. Qualitative KFLC oligoclonality was frequently observed in patients with IgG OCB (89.19%). Conclusions: KFLC are confirmed as a valuable complementary biomarker to IgG OCB in MS. K-index values should be evaluated in conjunction with clinical features, imaging data, and ongoing or prior treatments, as KFLC levels may be dynamic and treatment sensitive, with a potential risk of misclassification in diagnostically borderline cases.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
