Netherlands Institute for Neuroscience
Neuroimmunology

Author Of 2 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0119 - Neurofilament light chain levels correlate with lesion activity and axonal damage in MS (ID 902)

Speakers
Presentation Number
P0119
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

The level of neurofilament light chain (NfL), a major component of the neuronal cytoskeleton, in plasma or cerebrospinal fluid (CSF) is considered a promising biomarker in multiple sclerosis (MS) for inflammation-mediated axonal damage.

Objectives

The relation between NfL levels and MS specific neuropathological measures is not yet known, and is the subject of this study.

Methods

In this autopsy study (n=105), CSF NfL levels were measured using a Simoa assay and were correlated with hallmarks for acute and chronic damage axonal damage, clinical and pathological donor characteristics, and to proportions and activity of MS white matter lesions determined with myelin and HLA stainings.

Results

CSF NfL levels correlated with presence of acute axonal damage features (APP+ bulbs: p=0.04, APP+ axons: p=0.03) and correlated negatively with axonal density (Bielschowsky+ axons: p=8.3e-3) in the normal appearing pyramid tract. As CSF NfL levels were confounded by stroke (<1 year before death, p=2.0e-3), these donors were excluded from further MS specific clinical and neuropathological analysis. NfL correlated negatively with disease duration (p=6.9e-3), thus with more severe MS. NfL levels positively correlated with the proportion of active MS lesions containing foamy microglia (p=9.85e-10) and not those containing ramified microglia. NfL levels of donors without atrophy at neuropathological examination were positively correlated with the proportion of mixed lesions with foamy microglia (p=1.75e-3), and negatively correlated with the proportion of inactive lesions (p=5.66e-3) and remyelinated lesion presence (p=0.04).

Conclusions

We validated that CSF NfL levels reflect pathological hallmarks of acute disease activity and concomitant axonal degeneration. These observations support the clinical use of NfL to monitor these neuropathological processes in people with MS.

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Pathogenesis – Immunology Poster Presentation

P0935 - Absence of B cells in brainstem and white matter lesions associates with a less severe disease and absence of oligoclonal bands in MS autopsy cases (ID 939)

Speakers
Presentation Number
P0935
Presentation Topic
Pathogenesis – Immunology

Abstract

Background

Although meningeal B-cell infiltrates characterize progressive disease and cortical pathology in multiple sclerosis (MS), active and mixed active/inactive white matter lesions with lymphocytic infiltrates are also observed in advanced MS autopsy cases.

Objectives

We assessed the association between B-cell presence in brainstem and white matter lesions with pathological and clinical characteristics in MS autopsy cases.

Methods

Autopsy tissue of 140 MS and 24 control cases, as well as diagnostic biopsies of 24 MS patients were examined for CD20+ B cells and CD138+ plasma cells. Presence of these cells was compared to pathological and clinical characteristics. In corresponding cerebrospinal fluid (CSF) and plasma, immunoglobulin (Ig)G ratio and oligoclonal band (OCB) patterns were determined. In a clinical cohort of 73 patients, the presence of OCBs was determined at diagnosis and during follow-up.

Results

B cells were mostly found in the perivascular space and the meninges, but were also enriched in active and mixed active/inactive white matter MS lesions. In 34% of active and 71% of mixed active/inactive lesions, B cells were absent, which correlated with less pronounced meningeal B-cell infiltration. In an extreme of outcomes-analysis, donors without B cells or plasma cells at all locations analyzed, displayed a longer disease duration, less frequent secondary progressive MS, and a lower proportion of mixed active/inactive lesions when compared to donors with B cells and/or plasma cells at all locations. Moreover, a lower CSF IgG ratio and more frequent absence of OCBs were noted. In a clinical cohort, numbers of patients without OCBs in CSF were increased at follow-up.

Conclusions

Absence of B cells is associated with a favorable clinical and pathological profile. This finding may reflect extremes of a continuum of genetic or environmental constitution, but also a regression of white matter humoral immunopathology in the natural course of advanced MS.

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