Axonal and oligodendrocyte-localized IgM and IgG deposits in MS lesions

Sádaba, María C.; Tzartos, John; Paı́no, Carlos Luis; García-Villanueva, Mercedes; Álvarez‐Cermeño, José C.; Villar, Luisa M.; Esiri, Margaret M.

doi:10.1016/j.jneuroim.2012.03.020

Cited by 50 publications

(36 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…OCMB are present since MS onset and associate with an aggressive disease in terms of relapses [21], longterm disability [32] and brain atrophy progression [33]. These clinical features seem to be the result of the deleterious effect of IgM antibodies which have been found to bind to oligodendrocytes and axons in conjunction with C3b in MS brains [34]. These findings therefore support that autoantibodies contribute to MS progression by causing demyelination or axonal damage or by inhibiting remyelination, as suggested [30].…”

Section: Discussionmentioning

confidence: 60%

“…This issue was therefore investigated in our series. These clinical features seem to be the result of the deleterious effect of IgM antibodies which have been found to bind to oligodendrocytes and axons in conjunction with C3b in MS brains [34]. Interestingly, however, a higher frequency of OCMB was found in patients with elevated CSF NFL levels.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis

Villar

Picón

Costa‐Frossard

et al. 2014

Euro J of Neurology

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 94%

Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis

Villar

Picón

Costa‐Frossard

et al. 2014

Euro J of Neurology

View full text Add to dashboard Cite

show abstract

“…Indirect evidence for antibody-mediated damage was found in patients with IgM antibody deposition on myelin and demyelinated axons that colocalized with complement C3b next to antibody-antigen immuncomplexes in macrophages (Sadaba et al, 2012). In another distinct group of patients, oxidative stress may cause an oligodendrogliopathy that starts in the distal processes of oligodendrocytes with preferential loss of MAG and later results in apoptosis of the oligodendrocyte (pattern 3).…”

Section: Mechanisms Of Demyelinationmentioning

confidence: 99%

Inflammatory demyelinating diseases of the central nervous system

Höftberger

Lassmann

2018

Handbook of Clinical Neurology

135

106

View full text Add to dashboard Cite

Inflammatory demyelinating diseases are a heterogeneous group of disorders, which occur against the background of an acute or chronic inflammatory process. The pathologic hallmark of multiple sclerosis (MS) is the presence of focal demyelinated lesions with partial axonal preservation and reactive astrogliosis. Demyelinated plaques are present in the white as well as gray matter, such as the cerebral or cerebellar cortex and brainstem nuclei. Activity of the disease process is reflected by the presence of lesions with ongoing myelin destruction. Axonal and neuronal destruction in the lesions is a major substrate for permanent neurologic deficit in MS patients. The MS pathology is qualitatively similar in different disease stages, such as relapsing remitting MS or secondary or primary progressive MS, but the prevalence of different lesion types differs quantitatively. Acute MS and Balo's type of concentric sclerosis appear to be variants of classic MS. In contrast, neuromyelitis optica (NMO) and spectrum disorders (NMOSD) are inflammatory diseases with primary injury of astrocytes, mediated by aquaporin-4 antibodies. Finally, we discuss the histopathology of other inflammatory demyelinating diseases such as acute disseminated encephalomyelitis and myelin oligodendrocyte glycoprotein antibody-associated demyelination. Knowledge of the heterogenous immunopathology in demyelinating diseases is important, to understand the clinical presentation and disease course and to find the optimal treatment for an individual patient.

show abstract

“…However, in the NF‐L‐induced spasticity it was unclear whether the antibodies directed to NF‐L were themselves responsible for the pathogenicity in this model. In humans, it has recently been shown that IgG and IgM localize with neurofilaments in MS lesions . Nonetheless, the contribution of antibodies to NF‐L in MS remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…In humans, it has recently been shown that IgG and IgM localize with neurofilaments in MS lesions. 27 Nonetheless, the contribution of antibodies to NF-L in MS remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Neurofilament light as an immune target for pathogenic antibodies

et al. 2017

View full text Add to dashboard Cite

Antibodies to neuronal antigens are associated with many neurological diseases including paraneoplastic neurological disorders, epilepsy, amyotrophic lateral sclerosis and multiple sclerosis. Immunization with neuronal antigens such as neurofilament light (NF-L), a neuronal intermediate filament in axons, has been shown to induce neurological disease and spasticity in mice. Also, although antibodies to NF-L are widely used as surrogate biomarkers of axonal injury in amyotrophic lateral sclerosis and multiple sclerosis, it remains to be elucidated if antibodies to NF-L contribute to neurodegeneration and neurological disease. To address this, we examined the pathogenic role of antibodies directed to NF-L in vitro using spinal cord co-cultures and in vivo in experimental autoimmune encephalomyelitis (EAE) and optic neuritis animal models of multiple sclerosis. Here we show that peripheral injections of antibodies to NF-L augmented clinical signs of neurological disease in acute EAE, increased retinal ganglion cell loss in experimental optic neuritis and induced neurological signs following intracerebral injection into control mice. The pathogenicity of antibodies to NF-L was also observed in spinal cord co-cultures where axonal loss was induced. Taken together, our results reveal that as well as acting as reliable biomarkers of neuronal damage, antibodies to NF-L exacerbate neurological disease, suggesting that antibodies to NF-L generated during disease may also be pathogenic and play a role in the progression of neurodegeneration.

show abstract

Axonal and oligodendrocyte-localized IgM and IgG deposits in MS lesions

Cited by 50 publications

References 37 publications

Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis

Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis

Inflammatory demyelinating diseases of the central nervous system

Neurofilament light as an immune target for pathogenic antibodies

Contact Info

Product

Resources

About