Abstract
Cerebrospinal kappa free light chain (KFLC)-index is a marker of intrathecal immunoglobulin synthesis that aids in the diagnosis of multiple sclerosis (MS). However, little evidence exists on its prognostic role. Our aim is to analyze the relationship between KFLC-index and other MS biomarkers and to explore its prognostic role. This is a monocentric observational study in a cohort of 52 people with relapsing MS (pwRMS) performed on prospectively acquired clinical data and with retrospective evaluation of biomarkers. We measured KFLC-index, immunoglobulin intrathecal synthesis, cerebrospinal fluid (CSF) chitinase 3-like 1 (CHI3L1), and neurofilament light protein (NFL) and reviewed MRI to detect leptomeningeal contrast enhancement (LMCE). We compared time to Expanded Disability Status Scale (EDSS) 3 and to initiation of high-efficacy disease-modifying therapies (heDMTs) by multivariate Cox regression analysis. Median KFLC-index correlated with IgG/IgM indexes (p < 0.0001/p < 0.05) and IgG-oligoclonal bands (OCGBs) (p < 0.001). Patients with IgM-oligoclonal bands (OCMBs) had a higher KFLC-index (p = 0.049). KFLC-index was higher in patients with LMCE (p = 0.008) and correlated with CHI3L1 (p = 0.007), but disease activity had no effect on its value. Bivariate and multivariate analyses confirmed KFLC-index > 58 as an independent risk factor for reaching an EDSS of 3 (hazard ratio (HR) = 12.4; 95% CI = 1.1–147; p = 0.047) and for the need of treatment with heDMTs (HR = 3.0; 95% CI = 1.2–7.1; p = 0.0013). To conclude, our data suggest a potential prognostic role of the KFLC-index during the MS course.
Highlights
Multiple sclerosis (MS) has long been regarded as a T cellmediated disease
When we analyzed other cerebrospinal biomarkers such as neurofilament light protein (NFL) and chitinase 3-like 1 (CHI3L1), we only found a weak correlation between KFLCindex and CHI3L1 (r = 0.378; p = 0.007) (Figures 1E, F)
Regarding long-term prognosis, kappa free light chain (KFLC)-index correlated with CHI3L1, and its excess was related to the presence of IgM-oligoclonal bands (OCMBs) and leptomeningeal contrast enhancement (LMCE), biomarkers associated with worse outcomes, progressive disease, and gray matter pathology
Summary
Multiple sclerosis (MS) has long been regarded as a T cellmediated disease. increasing evidence supports the pathogenic role of B cells, through both the production of antibodies and the release of proinflammatory factors in the cerebrospinal fluid (CSF) [1]. Due to a predictive role in clinically isolated syndrome (CIS) conversion to MS, the examination of cerebrospinal IgGoligoclonal bands (OCGBs) has been reintroduced in the latest MS diagnostic criteria [5] This paradigm change has focused attention on other biomarkers related to immunoglobulin syntheses, such as kappa free light chains (KFLCs) and IgMoligoclonal bands (OCMBs). Interest in OCMBs, present in 48% of people with MS (pwMS), has been recently renewed after increased research supporting a correlation with unfavorable disease courses in MS [10–13] Considering this background, the present single-center observational study in relapsing MS (RMS) patients aims to assess the potential relationship between KFLC-index and other neuroinflammatory biomarkers, such as OCMBs, and its value as a complementary tool to OCGBs and as a risk factor for neurological disability and treatment failure
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