Increased kappa free light chain index in patients with late onset multiple sclerosis
Filipa Serrazina1, Alexandra Sofia Mendes2, Isabel Ribeiro Fonseca2
1Neurology Department, Hospital de Egas Moniz, ULSLO, Lisbon, Portugal.
Insights
Late-onset multiple sclerosis (MS) patients show a higher prevalence of increased kappa-free light chain (κFLC) index, indicating elevated intrathecal immunoglobulin synthesis. This finding may suggest a prolonged immune response in late-onset MS.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Multiple Sclerosis Pathogenesis
Background:
- Intrathecal immunoglobulin-G synthesis is a key feature of multiple sclerosis (MS).
- Cerebrospinal fluid (CSF) kappa-free light chain (κFLC) is a potential biomarker for MS, but its role in different patient subgroups requires further investigation.
Purpose of the Study:
- To compare intrathecal synthesis, measured by the κFLC index, between early-onset (EO) and late-onset (LO) MS patients.
- To investigate the diagnostic utility of the κFLC index in distinguishing between EO and LO MS.
Main Methods:
- Retrospective cohort study of 60 consecutively diagnosed MS patients.
- Measurement of κFLC levels in paired serum and CSF samples using nephelometry.
- Definition of increased κFLC index at ≥6.1, with patients categorized as EO (<50 years) or LO (≥50 years) at symptom onset.
Main Results:
- No significant differences in demographic or clinical variables were observed between EO and LO groups.
- The prevalence of CSF-restricted oligoclonal bands (OCB) was similar in both groups (88.6% EO vs. 88.0% LO).
- A significantly higher prevalence of an elevated κFLC index (≥6.1) was found in LO MS patients (88.0%) compared to EO MS patients (62.9%; p=0.040).
Conclusions:
- Late-onset MS patients exhibit a greater prevalence of elevated κFLC index, suggesting increased intrathecal immunoglobulin synthesis.
- This finding may indicate a more prolonged or intense intrathecal immune reaction in the pathogenesis of late-onset MS.
- The κFLC index may serve as a valuable biomarker for assessing intrathecal inflammation in distinct MS subgroups.
Introduction:
Intrathecal immunoglobulin-G synthesis is a pathological hallmark of multiple sclerosis (MS). Cerebrospinal fluid (CSF) kappa-free light chain (κFLC) detection has emerged as a new biomarker in MS, but little is known about its expression and variance across distinct patient subgroups.
Objective:
To assess and compare intrathecal synthesis through kFLC index between patients with early and late onset MS.
Methods:
An exploratory retrospective single-center cohort study including consecutively diagnosed MS patients was conducted. Nephelometric kFLC measurements of paired serum/CSF samples collected at MS diagnosis were obtained. A cut-off for increased κFLC index was established at ≥6.1 as per previous published reports. Two groups were defined: early onset (EO) patients (first MS symptoms < 50 years) and late onset (LO) patients (first MS symptoms ≥ 50 years).
Results:
Sixty (60) patients were included, 42(70 %) female, with a mean age of 48.3 years (±14.3; min18-max79) and a mean disease duration of 5.2 years (± 4.8; min 0.5-máx 23). 25 (41.7 %) LO patients were included. Groups did not differ in demographic or clinical variables. Although the prevalence of CSF-restricted OCB was similar between groups (EO n = 31, 88.6 %; LO n = 22, 88,0 %, p = 1.000), the prevalence of a kFLC index >6.1 was significantly higher in LO MS patients (n = 22, 88.0 % vs EO n = 22, 62,9 % p = 0.040).
Conclusion:
In this cohort, a higher prevalence of increased kFLC index was found among patients with late-onset MS. This may reflect a longer period of intrathecal dysimune reactions connected to MS pathological onset, even if not clinically expressed until later stages.
