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

Glehn, Felipe von; Farias, Alessandro S.; Oliveira, Augusto César Penalva de; Damasceno, Alfredo; Longhini, Ana Leda; Oliveira, E. Capelas de; Damasceno, Benito Pereira; Santos, Leonilda Maria Barbosa dos; Brandão, Carlos Otávio

doi:10.1177/1352458511428465

Cited by 53 publications

(42 citation statements)

References 11 publications

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“…2 Less knowledge exists about natalizumab interfering with intrathecal humoral immune activities. Recently, disappearance of oligoclonal bands (OCB) during natalizumab therapy in 4 out of 6 patients was reported from von Glehn et al 3 This is very interesting and substantiates the importance of investigating intrathecal antibody production in response to natalizumab treatment because, in contrast to other CNS diseases including neuromyelitis optica 4 , CSF-restricted OCB have been reported to persist in MS. 5,6 Since CSF data from patients during natalizumab therapy is scarce, we collected CSF data from several specialized MS centers to obtain an appropriate sample size for determining significant changes in CNS-restricted humoral immune activity attributable to natalizumab therapy. …”

Section: Introductionmentioning

confidence: 81%

Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy

et al. 2012

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Recently, the disappearance of oligoclonal bands (OCBs) from the cerebrospinal fluid (CSF) of a few natalizumab-treated patients with multiple sclerosis (MS) has been reported. This is interesting since CSF-restricted OCB are believed to persist in MS. We pooled CSF data from 14 MS centers to obtain an adequate sample size for investigating the suspected changes in central nervous system (CNS)-restricted humoral immune activities in the context of natalizumab therapy. In a retrospective chart analysis, CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy. At the time of repeat lumbar puncture, local IgG production (according to Reibergram) was significantly reduced (p < 0.0001) and OCB had disappeared in 16% of the patients. We therefore conclude that natalizumab therapy interferes with intrathecal antibody production at least in a significant number of patients. Recently, disappearance of oligoclonal bands (OCB) from the CSF of a few natalizumab-treated patients with MS has been reported. This is interesting since CSF-restricted OCB are considered to persists in MS.Since lumbar punctures during natalizumab therapy are infrequent we pooled CSF data from fourteen MS centers to obtain a suitable patient cohort for furhter investigations about the suspected impact of natalizumab on CNS-restricted humoral immune activities.In a retrospective chart analysis CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy.

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Section: Introductionmentioning

confidence: 81%

Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy

et al. 2012

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“…Inclusion of patients treated with immunomodulatory agents may also be considered problematic. Changes in o-IgG patterns after such therapies have been described by some authors [58][59][60] but not others 61,62 . It should be noted, however, that the only natalizumab-treated patient in our study had numerous CSF-restricted o-IgG (o-IgGκ only) as well as o-free κ (but no o-free λ) bands, and that we found no significant difference either in the numbers of CSF-restricted o-IgG or o-fLC bands or in the proportions of positive samples in treated and untreated MS patients (data not shown).…”

Section: Discussionmentioning

confidence: 97%

Oligoclonal free light chains in cerebrospinal fluid as markers of intrathecal inflammation. Comparison with oligoclonal IgG

Zeman¹,

Hradílek²,

Kušnierová³

et al. 2015

BIOMED PAP

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Aims.To compare the sensitivity and specificity of CSF-restricted oligoclonal IgG and free light chains as markers of multiple sclerosis and other inflammatory neurological diseases. Methods. 196 paired CSF and serum samples were examined for oligoclonal IgG and oligoclonal free light chains. The sensitivity and specificity of the tests were calculated and optimal cut-offs for the number of CSF-restricted oligoclonal bands were then determined by analysis of receiver operating characteristic curves. Results. Optimal cut-off values were ≥5 IgG bands for multiple sclerosis, ≥4 IgG bands for inflammatory neurological disease, ≥6 free κ, and ≥2 free λ bands for both purposes. Using these cut-off values, sensitivities and specificities for multiple sclerosis were 83.8% and 91.3% for IgG, 83.8% and 81.0% for free κ , and 67.6% and 75.4% for free λ. For inflammatory neurological disease, sensitivities and specificities were 60.8% and 95.7% for IgG, 69.6% and 92.6% for free κ, and 64.8% and 86.2% for free λ. Conclusions. Although exact cut-off values may vary according to method, reporting borderline results as positive, may compromise the specificity of the test and should be avoided.. The detection of intrathecal free light chain synthesis may be of value especially when the oligoclonal IgG test is negative or borderline, even though its specificity is slightly lower.

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“…In studies of CSF profiles in RRMS patients treated with natalizumab for at least 1 year, reductions were seen in CSF levels of CD4+ T cells, B cells (especially CD5+) and OCBs (IgM, and to a lesser extent, IgG) [Mancuso et al 2014;Villar et al 2012;Harrer et al 2013]; whereas OCBs reappeared in the CSF of patients who discontinued natalizumab [Harrer et al 2013;von Glehn et al 2012]. Similarly, a longitudinal study revealed that the CSF CD4+/CD8+ ratio, IgG and IgM levels and IgG-CSF index declined in samples collected during natalizumab treatment compared with pretreatment [Warnke et al 2015].…”

Section: Effects On Cns Cellular Infiltration and Intrathecal Antibodmentioning

confidence: 99%

Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

Sellebjerg

Cadavid

Steiner

et al. 2015

Ther Adv Neurol Disord

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Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events, including persistent microglial activation that may lead to chronic demyelination and neurodegeneration associated with irreversible disability. In patients with relapsing forms of MS, natalizumab therapy is known to significantly reduce intrathecal inflammatory responses which results in reductions in brain lesions and brain atrophy as well as beneficial effects on clinical measures, such as reduced frequency and severity of relapse and reduced accumulation of disability. Natalizumab treatment also reduces levels of cerebrospinal fluid chemokines and other biomarkers of intrathecal inflammation, axonal damage and demyelination, and has demonstrated the ability to reduce innate immune activation and intrathecal immunoglobulin synthesis in patients with MS. The efficacy of natalizumab therapy in SPMS is currently being investigated in a randomized, double-blind, placebo-controlled trial.

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

Cited by 53 publications

References 11 publications

Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy

Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy

Oligoclonal free light chains in cerebrospinal fluid as markers of intrathecal inflammation. Comparison with oligoclonal IgG

Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

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