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

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 856
Author(s):  
Diana Ferraro ◽  
Roberta Bedin ◽  
Patrizia Natali ◽  
Diego Franciotta ◽  
Krzysztof Smolik ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Oligoclonal Bands ◽  
Inflammatory Disorder ◽  
Kappa Index ◽  
Free Light Chains ◽  
Complementary Information ◽  
Albumin Ratio ◽  
Oligoclonal Igg ◽  
Csf Oligoclonal Bands ◽  
Oligoclonal Igg Bands

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.

The contribute of cerebrospinal fluid free light-chain assay in the diagnosis of multiple sclerosis and other neurological diseases in an Italian multicenter study

2021 ◽  
pp. 135245852110641
Author(s):  
Gaetano Bernardi ◽  
Tiziana Biagioli ◽  
Paola Malpassi ◽  
Teresa De Michele ◽  
Domizia Vecchio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disorders ◽  
Operating Characteristic ◽  
Neurological Diseases ◽  
Characteristic Curve ◽  
Oligoclonal Bands ◽  
Free Light Chains ◽  
Complementary Information ◽  
Combined Use

Background: Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus. Objective: To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases. Methods: A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite. Results: A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups ( p < 0.0001). The kFLC index ⩾ 6.4 is comparable to OCB for MS diagnosis (area under the receiver operating characteristic curve (AUC) = 0.876; sensitivity 83.6% vs 84.2%; specificity 88.5% vs 90.6%). λFLC index ⩾ 5 showed an AUC of 0.616, sensitivity of 33.3% and specificity of 90.6%. In all, 12/27 (44.4%) MS patients with negative OCB had kFLC index ⩾ 6.4. Interestingly, 37.5% of 24 patients with a single CSF IgG band showed high kFLC index and 12.5% positive λFLC index. Conclusion: Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.

Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid are less likely to develop neutralizing antibodies against interferon beta

2010 ◽  
Vol 16 (7) ◽  
pp. 796-800 ◽  
Author(s):  
M. Lundkvist ◽  
E. Greiner ◽  
J. Hillert ◽  
A. Fogdell-Hahn
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Oligoclonal Bands ◽  
Distinct Subgroup ◽  
Oligoclonal Igg ◽  
Multiple Sclerosis Patients ◽  
Genetically Determined ◽  
Oligoclonal Igg Bands

Multiple sclerosis patients without cerebrospinal fluid oligoclonal IgG bands have been proposed to constitute an immunogenetically distinct subgroup of multiple sclerosis that may also differ in terms of prognosis. A proportion of patients with multiple sclerosis receiving IFNβ develop neutralizing antibodies, which interfere with treatment efficacy. Evidence suggests that the likelihood of developing neutralizing antibodies is partly genetically determined. Here, we hypothesized that absence of oligoclonal IgG bands reflects a property of B-cell responses in oligoclonal IgG band-negative patients characterized by a lessened propensity to develop neutralizing antibodies. We aimed to compare the development of neutralizing antibodies against IFNβ between oligoclonal IgG band-negative and oligoclonal IgG band-positive multiple sclerosis patients. Treatment, oligoclonal IgG band and neutralizing antibody information was obtained for 2219 patients from the Swedish multiple sclerosis registry and the Swedish neutralizing antibody registry. Additional data on genotype was available for 532 patients. A correlation was found between oligoclonal IgG band negativity and neutralizing antibody negativity ( p = 0.02). This difference was confined to neutralizing antibodies against IFNβ-1a, since oligoclonal IgG band-negative patients were, to a lesser extent, neutralizing antibody positive compared with oligoclonal IgG band-positive patients if treated with IFNβ-1a (12% vs. 23%; p = 0.005). No difference was observed for IFNβ-1b-treated patients (44% vs. 46%). We propose that oligoclonal IgG band-negative patients differ immunologically from oligoclonal IgG band-positive patients, potentially influenced by distinct HLA-DRB1 alleles.

scholarly journals Multiple sclerosis in Brazil: analysis of cerebrospinal fluid by standard methods

1999 ◽  
Vol 57 (4) ◽  
pp. 927-931 ◽  
Author(s):  
MARZIA PUCCIONI-SOHLER ◽  
FABIOLA PASSER ◽  
CRISTIANE OLIVEIRA ◽  
CARLOS OTÁVIO BRANDÃO ◽  
REGINA PAPAIZ-ALVARENGA
Keyword(s):  
Multiple Sclerosis ◽  
Laboratory Parameter ◽  
Oligoclonal Bands ◽  
Local Production ◽  
Concerted Action ◽  
Standard Methods ◽  
Igg Synthesis ◽  
Intrathecal Igg Synthesis ◽  
Oligoclonal Igg ◽  
Oligoclonal Igg Bands

The demonstration of intrathecal IgG synthesis has been used as an important laboratory parameter to support the diagnosis of multiple sclerosis(MS). The Committee for European Concerted Action for Multiple Sclerosis has recommended a protocol for the assessment of intrathecal IgG synthesis. We applied this methodology to determine the cerebrospinal (CSF) profile of 128 Brazilian patients with MS. We detected hypercytosis lower than 35 cells/mm3 in 97%, protein lower than 80mg/dl in 99%, normal blood-CSF barrier function in 76%, increased IgG local production around 53% and oligoclonal IgG bands by isoelectric focusing in 85% of the definite MS patients. The diagnostic accuracy of the quantitative analysis was lower than the qualitative. The detection of oligoclonal bands was especially important in the cases of normal quantitative assays of IgG. In addition, we found a lower frequency of inflammatory reaction in CSF in our MS cases, in comparison to some European studies.

Clinical and laboratory features of neuromyelitis optica with oligoclonal IgG bands

2007 ◽  
Vol 13 (3) ◽  
pp. 332-335 ◽  
Author(s):  
M. Nakamura ◽  
I. Nakashima ◽  
S. Sato ◽  
I. Miyazawa ◽  
K. Fujihara ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Myasthenia Gravis ◽  
Neuromyelitis Optica ◽  
Disease Duration ◽  
Sicca Syndrome ◽  
Common Features ◽  
Laboratory Features ◽  
Oligoclonal Igg ◽  
Oligoclonal Igg Bands

Of 23 neuromyelitis optica (NMO) cases, we found two cases with oligoclonal IgG bands (OBs). Both patients were positive for NMO-IgG. Their common features were long disease duration and co-existing autoimmune diseases (myasthenia gravis and sicca syndrome). Although OBs are mostly negative in NMO, which distinguishes it from multiple sclerosis (MS), they can be positive by long-standing autoimmunity, which may not be directly related to NMO. Multiple Sclerosis 2007; 13: 332-335. http://msj.sagepub.com

Presence of CSF oligoclonal bands (OCB) is associated with the HLA-DRB1 genotype in a West Australian multiple sclerosis cohort

2010 ◽  
Vol 288 (1-2) ◽  
pp. 63-67 ◽  
Author(s):  
Jing-Shan Wu ◽  
Wei Qiu ◽  
Alison Castley ◽  
Ian James ◽  
Joyce Joseph ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Oligoclonal Bands ◽  
Csf Oligoclonal Bands

scholarly journals Oligoclonal IgG bands in the cerebrospinal fluid of portuguese patients with multiple sclerosis: negative results indicate benign disease

2005 ◽  
Vol 63 (2b) ◽  
pp. 375-379 ◽  
Author(s):  
Maria José Sá ◽  
Lucinda Sequeira ◽  
Maria Edite Rio ◽  
Edward J. Thompson
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Benign Disease ◽  
Serum Samples ◽  
Negative Results ◽  
Significant Difference ◽  
Relapsing Remitting ◽  
The Mean ◽  
Oligoclonal Igg ◽  
Oligoclonal Igg Bands

We assessed the frequency of cerebrospinal fluid (CSF) restricted oligoclonal IgG bands (IgG-OCB) in Portuguese multiple sclerosis (MS) patients and its relationship with outcome. Paired CSF/serum samples of 406 patients with neurological disorders were submitted to isoelectric focusing with immunodetection of IgG. Ninety-two patients had definite MS; non-MS cases were assembled in groups inflammatory/infectious diseases (ID, n=141) and other/controls (OD, n=173). We found in the MS group: mean duration, 38.9 months; clinically isolated syndromes, 24%; relapsing/remitting course (RR), 65%; in RR patients the mean EDSS was 2.1 and the mean index of progression was 0.31. Positive patterns significantly predominated in MS (82.6%; ID, 40.4%; OD, 3.5%). The sensitivity and the specificity of positive IgG-OCB for MS diagnosis was 82.6% and 79.9%, respectively. The sole statistically significant difference in the MS group was the lower progression index observed in negative cases. We conclude that the frequency of positive IgG-OCB patterns in our MS patients fits most values reported in the literature, and that negative results indicate benign disease.

scholarly journals Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis

2021 ◽  
Vol 11 (11) ◽  
pp. 1444
Author(s):  
Mattia Fonderico ◽  
Emilio Portaccio ◽  
Lorenzo Razzolini ◽  
Luisa Pastò ◽  
Angelo Bellinvia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Clinical Course ◽  
Meta Analysis ◽  
Clinically Isolated Syndrome ◽  
Relapsing Remitting ◽  
Oligoclonal Igg ◽  
Almost All ◽  
Present Systematic Review ◽  
Oligoclonal Igg Bands

The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.

Cerebrospinal fluid free kappa light chains and kappa index perform equal to oligoclonal bands in the diagnosis of multiple sclerosis

2018 ◽  
Vol 57 (2) ◽  
pp. 210-220 ◽  
Author(s):  
Mikael Christiansen ◽  
Mikkel Carstensen Gjelstrup ◽  
Morten Stilund ◽  
Tove Christensen ◽  
Thor Petersen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Sensitivity And Specificity ◽  
Diagnostic Performance ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Kappa Index ◽  
Absolute Concentration ◽  
Igg Index ◽  
The Absolute

AbstractBackgroundDetection of intrathecal immunoglobulin G (IgG) synthesis by gold standard oligoclonal bands (OCB) or IgG index remains an integral part of multiple sclerosis (MS) diagnostics, although both methods have weaknesses. Emerging evidence suggests that automated detection of free light chains (FLC) in the cerebrospinal fluid (CSF) has diagnostic performance equal to OCB. The objective of this study was to compare the diagnostic performance of CSF FLC with OCB and IgG index in a large cohort of Scandinavian patients referred for MS evaluation.MethodsWe prospectively included 230 patients suspected for MS. They are composed of patients with MS (n=96), clinically isolated syndrome (n=37), other neurological diseases (OND, n=31) and symptomatic controls (SC, n=66). CSF and serum samples were analyzed for kappa and lambda FLC, OCB and IgG index. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis.ResultsBoth the absolute concentration of CSF-kappa and the kappa index had excellent MS diagnostic performances with ROC area under the curve of 0.93 and 0.94 (MS vs. SC+OND). At the 0.42 mg/L cutoff, CSF-kappa had sensitivity and specificity of 93.8% and 85.6%, whereas sensitivity and specificity for OCB was 82.3% and 93.8% (72.9% and 95.9% for IgG index at cutoff 0.64). CSF-lambda and lambda index performed inferior to CSF-kappa and kappa index.ConclusionsCSF-kappa and kappa index represent automated, rapid and low-cost alternatives to OCB. Using merely the absolute concentration of CSF-kappa is a logistic advantage in the clinical laboratories.

Brainstem and cerebellar involvement in MOG-IgG-associated disorder versus aquaporin-4-IgG and MS

2020 ◽  
pp. jnnp-2020-325121
Author(s):  
Samantha A Banks ◽  
Padraig P Morris ◽  
John J Chen ◽  
Sean J Pittock ◽  
Elia Sechi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Aquaporin 4 ◽  
Oligoclonal Bands ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Middle Cerebellar Peduncle ◽  
Cerebellar Involvement ◽  
Cerebellar Peduncle ◽  
Csf Oligoclonal Bands

ObjectiveTo determine the frequency and characteristics of brainstem or cerebellar involvement in myelin-oligodendrocyte-glycoprotein-antibody-associated-disorder (MOGAD) versus aquaporin-4-IgG-seropositive-neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and multiple sclerosis (MS).MethodsIn this observational study, we retrospectively identified 185 Mayo Clinic MOGAD patients with: (1) characteristic MOGAD phenotype, (2) MOG-IgG seropositivity by live cell-based assay and (3) MRI lesion(s) of brainstem, cerebellum or both. We compared the symptomatic attacks to AQP4-IgG-NMOSD (n=30) and MS (n=30).ResultsBrainstem or cerebellar involvement occurred in 62/185 (34%) MOGAD patients of which 39/62 (63%) were symptomatic. Ataxia (45%) and diplopia (26%) were common manifestations. The median age in years (range) in MOGAD of 24 (2–65) was younger than MS at 36 (16–65; p=0.046) and AQP4-IgG-NMOSD at 45 (6–72; p=0.006). Isolated attacks involving the brainstem, cerebellum or both were less frequent in MOGAD (9/39 (23%)) than MS (22/30 (73%); p<0.001) but not significantly different from AQP4-IgG-NMOSD (14/30 (47%); p=0.07). Diffuse middle cerebellar peduncle MRI-lesions favoured MOGAD (17/37 (46%)) over MS (3/30 (10%); p=0.001) and AQP4-IgG-NMOSD (3/30 (10%); p=0.001). Diffuse medulla, pons or midbrain MRI lesions occasionally occurred in MOGAD and AQP4-IgG-NMOSD but never in MS. Cerebrospinal fluid (CSF) oligoclonal bands were rare in MOGAD (5/30 (17%)) and AQP4-IgG-NMOSD (2/22 (9%); p=0.68) but common in MS (18/22 (82%); p<0.001). Disability at nadir or recovery did not differ between the groups.ConclusionInvolvement of the brainstem, cerebellum or both is common in MOGAD but usually occurs as a component of a multifocal central nervous system attack rather than in isolation. We identified clinical, CSF and MRI attributes that can help discriminate MOGAD from AQP4-IgG-NMOSD and MS.

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