Cerebrospinal fluid free light chains compared to oligoclonal bands as biomarkers in multiple sclerosis

Gaetani, Lorenzo; Carlo, Marinella Di; Brachelente, Giovanni; Valletta, Federico; Mancini, Andrea; Gentili, Lucia; Borrelli, Antonio; Calabresi, Paolo; Sarchielli, Paola; Ferri, Carla; Villa, Alejandra

doi:10.1016/j.jneuroim.2019.577108

Cited by 43 publications

(37 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Diagnosis of MS relies on the so-called McDonald criteria, latest updated in 2017 (5). These criteria include detection of active inflammatory foci in the CNS as seen by positron emission tomography (PET) and magnetic resonance imaging (MRI) and intrathecal production of immunoglobulins (Igs), measured as an elevated cerebrospinal fluid (CSF)/serum IgG index, as a free light chain index or as the occurrence of oligoclonal bands (OCBs) of IgG in CSF (6)(7)(8)(9)(10). Each oligoclonal band is a result of intrathecal antibody (Ab) synthesis by single B cell clones and therefore, specific CSF/ serum Ab indices (AIs) may also be elevated, e.g., Abs to various viruses, corresponding to the specificity of some of the OCBs (11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus and Multiple Sclerosis

2020

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a neurologic disease affecting myelinated nerves in the central nervous system (CNS). The disease often debuts as a clinically isolated syndrome, e.g., optic neuritis (ON), which later develops into relapsing-remitting (RR) MS, with temporal attacks or primary progressive (PP) MS. Characteristic features of MS are inflammatory foci in the CNS and intrathecal synthesis of immunoglobulins (Igs), measured as an IgG index, oligoclonal bands (OCBs), or specific antibody indexes. Major predisposing factors for MS are certain tissue types (e.g., HLA DRB1*15:01), vitamin D deficiency, smoking, obesity, and infection with Epstein-Barr virus (EBV). Many of the clinical signs of MS described above can be explained by chronic/recurrent EBV infection and current models of EBV involvement suggest that RRMS may be caused by repeated entry of EBV-transformed B cells to the CNS in connection with attacks, while PPMS may be caused by more chronic activity of EBV-transformed B cells in the CNS. In line with the model of EBV’s role in MS, new treatments based on monoclonal antibodies (MAbs) targeting B cells have shown good efficacy in clinical trials both for RRMS and PPMS, while MAbs inhibiting B cell mobilization and entry to the CNS have shown efficacy in RRMS. Thus, these agents, which are now first line therapy in many patients, may be hypothesized to function by counteracting a chronic EBV infection.

show abstract

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus and Multiple Sclerosis

2020

View full text Add to dashboard Cite

show abstract

“…Various studies comparing the diagnostic accuracy of the kappa index and OCB for a MS diagnosis found similar results, with the kappa index being slightly more sensitive and less specific compared to OCB [ 8 , 9 , 10 , 11 ], although not all studies are concordant [ 12 , 13 , 14 ]. The sensitivity and specificity of both kappa index and OCB found in the present study was lower compared to the existing literature, which reports values up to 100% for either sensitivity or specificity [ 15 ].…”

Section: Discussionmentioning

confidence: 87%

Kappa Index versus CSF Oligoclonal Bands in Predicting Multiple Sclerosis and Infectious/Inflammatory CNS Disorders

et al. 2020

View full text Add to dashboard Cite

Background: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID). Methods: We enrolled patients who underwent a diagnostic spinal tap throughout two years. KFLC levels were determined using a Freelite assay (Binding Site) and the turbidimetric Optilite analyzer. Results: Of 540 included patients, 223 had a CNSID, and 84 had MS. The kappa index was more sensitive (0.89 versus 0.85) and less specific (0.84 versus 0.89), with the same AUC (0.87) as OCB for MS diagnosis (optimal cut-off: 6.2). Adding patients with a single CSF IgG band to the OCB-positive group slightly increased the AUC (0.88). Likewise, the kappa index (cut-off: 3.9) was more sensitive (0.67 versus 0.50) and less specific (0.81 versus 0.97), with the same AUC (0.74) as OCB, for a CNSID diagnosis. Conclusion: The kappa index and CSF OCB have comparable diagnostic accuracies for a MS or CNSID diagnosis and supply the clinician with useful, complementary information.

show abstract

“…In a recent study by Gaetani and coworkers, KFLC index distinguished precisely as did IgG OCB between MS and non-inflammatory diseases using a cut-off value of 7.83 [56] . It has been suggested that a higher cut-off value (10.6) could be useful to differentiate MS from other inflammatory diseases by increasing specificity and to predict conversion in CIS with greater accuracy as compared with OCB [56] . Similarly, high levels of CSF KFLC have also been demonstrated in CIS patients, showing a correlation with the risk of conversion to clinically definite MS within 2 years [43,60] .…”

Section: Kappa Free Light Chains and Kappa Indexmentioning

confidence: 98%

“…Although different thresholds have been used in several studies, ranging from 4.25 [55] to 12.3 [53] , KFLC index extensively proved to have a higher sensitivity and a lower specificity with a similar diagnostic accuracy compared with IgG OCB in discriminating MS and controls [53,[55][56][57][58][59] . In a recent study by Gaetani and coworkers, KFLC index distinguished precisely as did IgG OCB between MS and non-inflammatory diseases using a cut-off value of 7.83 [56] . It has been suggested that a higher cut-off value (10.6) could be useful to differentiate MS from other inflammatory diseases by increasing specificity and to predict conversion in CIS with greater accuracy as compared with OCB [56] .…”

Section: Kappa Free Light Chains and Kappa Indexmentioning

confidence: 99%

“…It has been hypothesized that KFLC index may replace IgG index as a first-line test, but some disagreement remains about the need to determine both KFLC index and IgG OCB in patients with suspected MS [63] or to use them sequentially [56] . Probably, the higher sensitivity of KFLC index compared with IgG OCB would allow clinicians to screen patients in a shorter time, with lower costs and the advantage of a quantitative assessment [49,58] , restricting the use of IgG OCB to patients with positive KFLC index.…”

Section: Kappa Free Light Chains and Kappa Indexmentioning

confidence: 99%

See 1 more Smart Citation

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Toscano¹,

Patti²

2020

View full text Add to dashboard Cite

For many years, quantifiable biomarkers in neurological diseases have represented a hot topic. In multiple sclerosis (MS), cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's criteria in 1983, with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and a complementary one after the introduction of McDonald criteria in 2001. Nowadays, that supporting role has turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with a first clinical event, according to the 2017 revised McDonald criteria. Possibly kappa free light chains, N-CAM, chitinase 3-like protein 1 and IgM oligoclonal bands, not yet implemented in clinical practice, could similarly gain importance in the near future. Furthermore, the increasing knowledge of molecular mechanisms leading to chronic inflammation has enhanced interest in looking for biomarkers of disease activity, better defining the MS phenotype and patients with highly active disease. Accordingly, myelin proteins, intermediate filaments, metalloproteinases and other molecules involved in the inflammatory cascade, are currently under investigation. Finally, it has long been known that axonal loss occurs from the early phases, leading to a progressive neurological deterioration. Since established criteria to assess treatment failure and transition to progressive forms are still lacking, both treatment response and prognostic biomarkers would be useful to predict MS course, and neurofilaments seem to have this potential. The purpose of this review article was to illustrate biomarkers that have been already validated or require further validation after proving to be useful in exploratory studies and potentially could prove useful in clinical practice in the coming years.

show abstract

Cerebrospinal fluid free light chains compared to oligoclonal bands as biomarkers in multiple sclerosis

Cited by 43 publications

References 27 publications

Epstein-Barr Virus and Multiple Sclerosis

Epstein-Barr Virus and Multiple Sclerosis

Kappa Index versus CSF Oligoclonal Bands in Predicting Multiple Sclerosis and Infectious/Inflammatory CNS Disorders

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Contact Info

Product

Resources

About