Clinical and cognitive implications of cerebrospinal fluid oligoclonal bands in multiple sclerosis patients

Anagnostouli, Maria; Christidi, Foteini; Zalonis, Ioannis; Nikolaou, Chryssoula; Lyrakos, Dimitrios G.; Triantafyllou, Nikolaos; Evdokimidis, Ioannis; Kilidireas, Constantinos

doi:10.1007/s10072-015-2303-1

Cited by 17 publications

(11 citation statements)

References 48 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The variation in seroprevalence of CSF-OCB could be related to different study designs and studied population 19 . In clinical aspects, OCB-positive and OCB-negative groups were similar, which is in line with most previous studies 20 .…”

Section: Discussionsupporting

confidence: 92%

Advanced MRI features in relapsing multiple sclerosis patients with and without CSF oligoclonal IgG bands

Zhao

Abrigo

Chen

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Oligoclonal IgG bands (OCB) in cerebrospinal fluid (CSF) are important in diagnosis of multiple sclerosis (MS). We evaluated the MRI features of clinically definite MS subjects with and without CSF-OCB. Relapsing MS subjects were recruited from a prospective registry in a university center. CSF-OCB were detected using isoelectric focusing and lgG-specific immunofixation. MRI metrics including brain volumes, lesion volumes and microstructural measures, were analyzed by fMRiB Software Library (fSL) and Statistical parametric Mapping (SpM). Seventy-five subjects with relapsing MS were analyzed. Forty-four (59%) subjects had an interval MRI at around 1 year. CSF-OCB were detected in 46 (61%) subjects. The OCB-positive group had a higher proportion of cerebellar lesions than the OCB-negative group (23.9% vs. 3.4%, p = 0.057). Except for amygdala volumes which were lower in the OCB-positive group (p = 0.034), other regional brain volumes including the subcortical deep gray matter and corpus callosum were similar. the two groups also showed comparable brain atrophy rate. For DTI, the OCB-positive group showed significantly higher mean diffusivity (MD) value in perilesional normal-appearing white matter (p = 0.043). Relapsing MS patients with and without CSF-OCB shared similar MRi features regarding volumetric analyses and Dti microstructural integrity. Oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF) are one of the most sensitive biomarkers in the diagnostic work-up of multiple sclerosis (MS), and inclusion of their presence into the updated McDonald criteria has improved clinical diagnosis 1. Up to 95% of Caucasian patients and 60% of Asian patients with MS are positive for CSF-OCB 2,3. Limited data support that CSF-OCB may be involved in the pathogenesis of MS; some pathological studies revealed that tissue damage may be underpinned by other types of oligoclonal bands such as IgM 4. Meanwhile, the relationship between CSF-OCB status and disease characteristics, such as clinical course, disease progression, responses to disease modifying therapies, remain unclear 3,5. Magnetic resonance imaging (MRI) is now standard of care in the management of MS, allowing diagnosis and monitoring of treatment response in clinical practice 6. Compared to conventional MRI alone, the use of high-resolution images, advanced pulse sequences and advanced computational techniques provides a more comprehensive information on the pathophysiological extent of disease. For instance, volumetric imaging allows a more precise quantitative assessment of brain atrophy which in turn has been shown to occur early in the disease course and is associated with disease progression of MS 7,8. Recent clinical trials have incorporated brain atrophy, at an annual brain volume loss (BVL) rate threshold of 0.4%, as a secondary outcome measure and marker of neurodegeneration in MS 9. Meanwhile, diffusion tensor imaging (DTI) allows microstructural assessment of white matter integrity by quantifying the magnitude and directionality of the molecular di...

show abstract

Section: Discussionsupporting

confidence: 92%

Advanced MRI features in relapsing multiple sclerosis patients with and without CSF oligoclonal IgG bands

Zhao

Abrigo

Chen

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Persistent intrathecal inflammation, demonstrated by the presence of OCBs in the CSF (25), is one of the hallmarks of MS in up to 95% of patients (25,26). Previous research demonstrated that the presence of CSF-OCBs in patients with MS tends to be related to widespread cognitive changes, especially worse visual memory (27) and larger periventricular lesion area on MRI (28). However, data on the relationship between inflammatory markers, such as CSF-OCBs or elevated IgG indices, and neurodegenerative markers, such as brain atrophy markers or RNFL thickness, in MS are limited (27).…”

Section: Introductionmentioning

confidence: 99%

Cognitive Decline in Multiple Sclerosis Is Related to the Progression of Retinal Atrophy and Presence of Oligoclonal Bands: A 5-Year Follow-Up Study

et al. 2021

View full text Add to dashboard Cite

Background: Brain atrophy, which is associated with cognitive impairment and retinal nerve fiber layer (RNFL) atrophy, is the main biomarker of neurodegeneration in multiple sclerosis (MS). However, data on the relationship between inflammatory markers, such as oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF), and cognition, RNFL atrophy, and brain atrophy are scarce. The aim of this study was to assess the influence of RNFL thickness, brain atrophy markers, intrathecal OCBs, and the immunoglobulin G (IgG) index on cognitive decline over a 5-year period in patients with MS.Methods: This prospective, single-center, observational cohort study included 49 patients with relapsing MS followed up over 5 years. At baseline, the patients underwent brain magnetic resonance imaging (MRI). Cognitive evaluation was performed using the Brief International Cognitive Assessment for MS (BICAMS), and RNFL thickness was assessed using optical coherence tomography (OCT). OCBs and IgG levels in the CSF were evaluated at baseline. The BICAMS, OCT, and MRI findings were re-evaluated after 5 years.Results: A significant reduction in information processing speed, visual learning, temporal RNFL thickness, the Huckman index, and third ventricle mean diameter was found in all 49 patients with relapsing MS over the observation period (p < 0.05). Of the patients, 63.3% had positive OCBs and 59.2% had elevated IgG indices. The atrophy of the temporal segment and papillomacular bundle and the presence of OCBs were significantly related to a decline in information processing speed in these patients (p < 0.05). However, brain atrophy markers were not found to be significant on the general linear models.Conclusions: RNFL atrophy and the presence of OCBs were related to cognitive decline in patients with MS over a 5-year follow-up period, thereby suggesting their utility as potential biomarkers of cognitive decline in MS.

show abstract

“…Electrophoretically homogeneous IgGs were obtained using first affinity chromatography of the serum and CSF proteins on protein G-Sepharose and then by FPLC gel filtration as in [17][18][19]. The content of IgGs in serum and CSF of different patients as well as their concentration after their purification was estimated by standard immunochemical nephelometry according to [7][8][9]33,34].…”

Section: Purification Of Iggsmentioning

confidence: 99%

“…The isofocusing profiles DNase, MBP-, and histone-hydrolyzing activities of IgGs may be very different for various individuals, but the total IgG subfractions with all their activities are distributed from pH 3 to 10. and bacteria, at first there is an accumulation of antibodies against their components, which may have structural similarities with the components of blood and human cells [3,4]. Then, due to the mimicry of certain proteins of viruses and bacteria with those of humans, epitope spreading and bystander activation, a failure of the immune system can occur leading to the generation of Abs against its own components of the human body and, as a result, to the development of MS.One of the features of MS is the appearance of oligoclonal IgGs in the bone marrow CSF, revealing themselves as oligoclonal bands (OCBs) after CSF proteins isofocusing [5][6][7]. Nevertheless, OCBs were found in the CSF of patients with MS who were sick and non-sick with various bacterial and viral diseases.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Extreme Diversity of IgGs Against Histones, DNA, and Myelin Basic Protein in the Cerebrospinal Fluid and Blood of Patients with Multiple Sclerosis

et al. 2020

View full text Add to dashboard Cite

It was recently shown that IgGs from sera of multiple sclerosis (MS) patients are active in the hydrolysis of DNA and myelin basic protein (MBP). We first analyzed the relative concentration of antibodies against five histones (H1, H2a, H2b, H3, and H4) in the cerebrospinal fluid (CSF) and serum of patients with MS. The relative concentrations of blood and CSF IgGs against histones and their activity in the hydrolysis of five histones varied greatly from patient to patient. However, all 28 IgG preparations were hydrolyzed from one to five histones. Relative activities and correlation coefficients among the activities of IgGs from serum and CSF in the hydrolysis of five histones (H1, H2a, H2b, H3, and H4), DNA, and MBP were calculated. It was shown that auto-IgGs from CSF and sera of MS patients are extremely heterogeneous in their affinity to histones, MBP, and DNA. The heterogeneity of IgG-abzymes hydrolyzing DNA, MBP, and histones from CSF and sera was also demonstrated using their isoelectrofocusing. The isofocusing profiles DNase, MBP-, and histone-hydrolyzing activities of IgGs may be very different for various individuals, but the total IgG subfractions with all their activities are distributed from pH 3 to 10.

show abstract

Clinical and cognitive implications of cerebrospinal fluid oligoclonal bands in multiple sclerosis patients

Cited by 17 publications

References 48 publications

Advanced MRI features in relapsing multiple sclerosis patients with and without CSF oligoclonal IgG bands

Advanced MRI features in relapsing multiple sclerosis patients with and without CSF oligoclonal IgG bands

Cognitive Decline in Multiple Sclerosis Is Related to the Progression of Retinal Atrophy and Presence of Oligoclonal Bands: A 5-Year Follow-Up Study

Extreme Diversity of IgGs Against Histones, DNA, and Myelin Basic Protein in the Cerebrospinal Fluid and Blood of Patients with Multiple Sclerosis

Contact Info

Product

Resources

About