Diagnostic Cerebrospinal Fluid Biomarker in Early and Late Onset Multiple Sclerosis

Abstract

Background: The intrathecal humoral response is the characteristic diagnostic finding in the cerebrospinal fluid (CSF) analysis of patients with multiple sclerosis (MS). Although the average age of MS patients increases, little is known about the sensitivity of diagnostic markers in elderly MS patients. Methods: In this retrospective two-center study, intrathecal free light chains kappa fraction (FLCk IF) and oligoclonal bands (OCB) were studied in a large cohort of patients with early and late onset relapsing (RMS) and progressive (PMS) MS. Furthermore, the humoral immune profile in CSF was analyzed, including the polyspecific intrathecal immune response measured as the MRZ reaction. Results: While the frequency of CSF-specific OCB did not differ between early and late onset RMS and PMS, the sensitivity of positive FLCk IF and absolute FLCk IF values were lower in PMS. The positivity of the MRZ reaction was equally frequent in early and late onset RMS and PMS. PMS patients had higher local IgA concentrations than RMS patients (p = 0.0123). Conclusions: OCB are slightly superior to FLCk IF in progressive MS in terms of sensitivity for detecting intrathecal immunoglobulin synthesis. The MRZ reaction, as the most specific parameter for MS, is also applicable in patients with late onset and progressive MS.

Establishing the best combination of the kappa free light chain index and oligoclonal bands for an accurate diagnosis of multiple sclerosis

“…To mitigate bias, we excluded patients with undetectable CSF KFLC concentrations for whom the KFLC index yielded high values (4.9% from the total cohort). Second, several pre-analytical factors might affect the levels of CSF KFLCs and thus the KFLC index (5), e.g., late-onset (>50 years) progressive MS (37), renal dysfunction (38), blood contamination of CSF (39), storage or treatment of samples (40), and several therapies used to treat relapses, such as corticosteroids, intravenous immunoglobulins, or plasmapheresis (40). Furthermore, highlyeffective DMTs might also decrease levels of the KFLC index (41), unlike other therapies (10,42).…”

Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers

“…Although multiple functions for B cells in MS have been proposed, the role of antibody-producing B cells and the identification of their MS-associated autoantibodies remain unknown ( 5 ). What is certain is that the cerebrospinal fluid (CSF) of patients with MS is characterized by deposition of clonally expanded immunoglobulins (Igs) ( 6 ), termed oligoclonal bands (OCBs), which are considered the hallmark biomarker for an MS diagnosis ( 7 ). The presence of OCBs has been classically associated with an intrathecal clonal expansion of B cells that contribute to the production of these autoreactive antibodies within the CNS ( 8 ).…”