Discontinuos distribution of IgG oligoclonal bands in cerebrospinal fluid from multiple sclerosis patients

Retrospective studies show that natalizumab modifies oligoclonal immunoglobulin (IgG) bands (OCBs) in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. In this study, we prospectively analyzed both serum and CSF samples from 24 MS patients, before and after 2 years of natalizumab-based therapy. Our results showed complete (55%) or partial (27%) disappearance of the OCBs in CSF samples that were taken after 2 years of therapy. Intrathecal IgG production, represented by the IgG index and IgGLoc, was also quantitatively reduced. Our data showed that natalizumab substantially modulates both intrathecal polyclonal and oligoclonal IgG production: This effect was much more potent than was previously reported.

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Disappearance of cerebrospinal fluid oligoclonal bands after natalizumab treatment of multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458511428465 ◽

2011 ◽

Vol 18 (7) ◽

pp. 1038-1041 ◽

Cited By ~ 35

Author(s):

Felipe von Glehn ◽

Alessandro S Farias ◽

Augusto C Penalva de Oliveira ◽

Alfredo Damasceno ◽

Ana Leda F Longhini ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Oligoclonal Bands ◽

Natalizumab Treatment ◽

The Central Nervous System ◽

Immunologic Abnormality ◽

Csf Oligoclonal Bands ◽

Multiple Sclerosis Patients

Intrathecal immunoglobulin synthesis in an oligoclonal pattern is the most common immunologic abnormality detected in MS patients. Various treatments, such as immunomodulators and immunosuppressors, have not been found to modify it. Natalizumab hinders migration of encephalitogenic T-cells into the central nervous system (CNS), reducing inflammatory response. Its impact on CSF oligoclonal bands (OCBs) has not been demonstrated. This report describes its effect in four out of six patients with multiple sclerosis after a mean of 10 infusions: the CSF was negative for OCBs at the second lumbar puncture. In conclusion, natalizumab treatment can reduce CSF OCBs to undetectable levels, although the clinical significance of this observation is not yet known.

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Oligoclonal bands in cerebrospinal fluid detected by PhastSystem isoelectric focusing

Clinical Chemistry ◽

10.1093/clinchem/36.1.123 ◽

1990 ◽

Vol 36 (1) ◽

pp. 123-125 ◽

Cited By ~ 8

Author(s):

I Wybo ◽

M Van Blerk ◽

R Malfait ◽

P Goubert ◽

F Gorus

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Cerebrospinal Fluid ◽

Isoelectric Focusing ◽

Protein Electrophoresis ◽

Oligoclonal Bands ◽

Agarose Gels ◽

Oligoclonal Banding ◽

The Central Nervous System ◽

Multiple Sclerosis Patients

Abstract Pharmacia's "PhastSystem" for semi-automated isoelectric focusing (IEF) in thin precast polyacrylamide gels (PAGE) was found to be as sensitive as high-resolution protein electrophoresis (HRPE) in agarose gels and conventional PAGE-IEF for detection of oligoclonal banding (OB) in concentrated cerebrospinal fluid (CSF) samples. Both PhastSystem IEF and HRPE revealed OB in CSF from eight of nine multiple sclerosis patients and four of 10 patients with various types of infection of the central nervous system as opposed to only two of 70 patients with miscellaneous neuropsychiatric disorders. The PhastSystem also frequently detected OB in silver-stained, unconcentrated CSF from patients with multiple sclerosis.

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Study of oligoclonal bands restricted to the cerebrospinal fluid in multiple sclerosis patients in the city of São Paulo

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2009000600011 ◽

2009 ◽

Vol 67 (4) ◽

pp. 1017-1022 ◽

Cited By ~ 12

Author(s):

Paulo Diniz da Gama ◽

Luís dos Ramos Machado ◽

José Antonio Livramento ◽

Hélio Rodrigues Gomes ◽

Tarso Adoni ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Sao Paulo ◽

Oligoclonal Bands ◽

Control Group ◽

São Paulo ◽

The Central Nervous System ◽

Different Populations ◽

Multiple Sclerosis Patients ◽

The City

The frequency of oligoclonal bands (OCB) restricted to the cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) varies widely in different populations. The objective of this study was to determine the frequency of these OCB in a group of MS patients in the city of São Paulo. Techniques used to detect OCB consisted of isoelectric focusing followed by immunoblotting. Oligoclonal bands were found in 49 (54.4%) out of 90 patients with clinically definite MS; in (31.2%) of the 16 patients with clinically isolated syndrome; in 7 (17.9%) of 39 patients with inflammatory disorders of the central nervous system (IDCNS), and in none of the individuals with no neurological condition (control group). The specificity of the method was 100% when compared to the control group and 82.1% when compared to the IDCNS group. These results suggest that the frequency of CSF OCB is much lower in Brazilian MS patients from São Paulo city than that reported in MS series from Caucasian populations.

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Relative value of three laboratory methods in the diagnosis of multiple sclerosis.

Clinical Chemistry ◽

10.1093/clinchem/27.12.2011 ◽

1981 ◽

Vol 27 (12) ◽

pp. 2011-2013 ◽

Cited By ~ 10

Author(s):

L C Bloomer ◽

P F Bray

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Laboratory Data ◽

Oligoclonal Bands ◽

Serum Samples ◽

Relative Value ◽

Definite Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Positive Results

Abstract We compared three methods of analysis for IgG in cerebrospinal fluid, using samples from 158 patients with clinically suspected multiple sclerosis and from 200 neurological controls. The tests were: search for oligoclonal bands, calculation of rate of synthesis of IgG in the cerebrospinal fluid, and determination of the IgG/albumin ratio. Paired cerebrospinal fluid and serum samples were collected and their IgG and albumin concentrations measured. Oligoclonal bands were detected by electrophoresis on agarose. Positive results were obtained in 94, 75, and 67% of patients with probable or definite multiple sclerosis by the three respective methods. In contrast, for patients for whom the clinical diagnosis of multiple sclerosis was considered possible, positive results were obtained in 10, 43, and 13%, respectively. Evidently, detection of oligoclonal bands remains the best single test for the presence of abnormal IgG in suspected multiple sclerosis patients. A combination of the first two tests is most sensitive for both probable and definite multiple sclerosis (97%) and possible multiple sclerosis (50%). Some infectious or immunologic disorders can also produce these IgG abnormalities, but they can usually be distinguished from multiple sclerosis by other clinical and laboratory data.

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Cytokines and intrathecal IgG synthesis in multiple sclerosis patients during clinical remission

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2005000600002 ◽

2005 ◽

Vol 63 (4) ◽

pp. 914-919 ◽

Cited By ~ 18

Author(s):

Carlos Otávio Brandão ◽

Heloísa Helena Ruocco ◽

Alessandro dos Santos Farias ◽

Celina Oliveira ◽

Dannie Eiko Maeda Hallal-Longo ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Proinflammatory Cytokines ◽

Clinical Remission ◽

Cytokine Production ◽

Inflammatory Activity ◽

Oligoclonal Bands ◽

Igg Synthesis ◽

Intrathecal Igg Synthesis ◽

Multiple Sclerosis Patients

Cytokines and intrathecal IgG synthesis were determined in the cerebrospinal fluid (CSF) and sera to evaluate inflammatory activity in multiple sclerosis (MS) patients during clinical remission. Although the disease was stable, there had been a significant increase of proinflammatory cytokines such as TNFalpha and IFNgamma in the CSF and serum, with no significant changes of IL12 and IL10 production. The changes in the cytokine production patterns were associated with an increase of leukocytes in the CSF, as well as the presence of oligoclonal bands suggesting intrathecal IgG synthesis. These results suggest that even when the disease is clinically silent, one can observe inflammatory activity in these MS patients.

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Disappearance of Cerebrospinal Fluid Oligoclonal Bands after Natalizumab Treatment of Multiple Sclerosis Patients (P02.136)

Neurology ◽

10.1212/wnl.78.1_meetingabstracts.p02.136 ◽

2012 ◽

Vol 78 (Meeting Abstracts 1) ◽

pp. P02.136-P02.136

Author(s):

F. Von Glehn Silva ◽

A. Farias ◽

A. Penalva-de-Oliveira ◽

A. Damasceno ◽

A. L. Longhini ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Oligoclonal Bands ◽

Natalizumab Treatment ◽

Multiple Sclerosis Patients

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Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid have less global and regional brain atrophy

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2014.06.010 ◽

2014 ◽

Vol 274 (1-2) ◽

pp. 149-154 ◽

Cited By ~ 29

Author(s):

Daniel Ferreira ◽

Olga Voevodskaya ◽

Kerstin Imrell ◽

Leszek Stawiarz ◽

Gabriela Spulber ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Brain Atrophy ◽

Oligoclonal Bands ◽

Regional Brain ◽

Multiple Sclerosis Patients ◽

Regional Brain Atrophy

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

Multiple Sclerosis Journal ◽

10.1177/1352458510373112 ◽

2010 ◽

Vol 16 (7) ◽

pp. 796-800 ◽

Cited By ~ 15

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.

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