Uncontrolled inflammation of the nervous system

Yüksel, Deniz; Oğuz, Kader K.; Azapağası, Ebru; Kesici, Selman; Çavdarlı, Büşranur; Konuşkan, Bahadır; Topaloǧlu, Haluk

doi:10.1212/cpj.0000000000000511

Cited by 9 publications

(9 citation statements)

References 8 publications

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“…Moreover, the MAC endogenous inhibitor CD59 is expressed by neurons [ 67 ] and astrocytes [ 67 , 68 ], likely to protect them from uncontrolled neuroinflammation [ 69 , 70 ]. CD59 deficiency causes catastrophic neuroinflammatory conditions [ 71 , 72 , 73 ]. In AD, protein levels of CD59 and other complement inhibitors are diminished, whereas those of the complement effectors increased [ 70 , 74 ], rendering neurons susceptible to complement attack [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

Astrocyte- and Neuron-Derived Extracellular Vesicles from Alzheimer’s Disease Patients Effect Complement-Mediated Neurotoxicity

Nogueras-Ortiz

Mahairaki²,

Delgado-Peraza

et al. 2020

Cells

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We have previously shown that blood astrocytic-origin extracellular vesicles (AEVs) from Alzheimer’s disease (AD) patients contain high complement levels. To test the hypothesis that circulating EVs from AD patients can induce complement-mediated neurotoxicity involving Membrane Attack Complex (MAC) formation, we assessed the effects of immunocaptured AEVs (using anti-GLAST antibody), in comparison with neuronal-origin (N)EVs (using anti-L1CAM antibody), and nonspecific CD81+ EVs (using anti-CD81 antibody), from the plasma of AD, frontotemporal lobar degeneration (FTLD), and control participants. AEVs (and, less effectively, NEVs) of AD participants induced Membrane Attack Complex (MAC) expression on recipient neurons (by immunohistochemistry), membrane disruption (by EthD-1 assay), reduced neurite density (by Tuj-1 immunohistochemistry), and decreased cell viability (by MTT assay) in rat cortical neurons and human iPSC-derived neurons. Demonstration of decreased cell viability was replicated in a separate cohort of autopsy-confirmed AD patients. These effects were not produced by CD81+ EVs from AD participants or AEVs/NEVs from FTLD or control participants, and were suppressed by the MAC inhibitor CD59 and other complement inhibitors. Our results support the stated hypothesis and should motivate future studies on the roles of neuronal MAC deposition and AEV/NEV uptake, as effectors of neurodegeneration in AD.

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Section: Discussionmentioning

confidence: 99%

Astrocyte- and Neuron-Derived Extracellular Vesicles from Alzheimer’s Disease Patients Effect Complement-Mediated Neurotoxicity

Nogueras-Ortiz

Mahairaki²,

Delgado-Peraza

et al. 2020

Cells

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“…1 Primary involvement of the CNS parenchyma is rare and has been reported in one family from Turkey where two siblings, one with acute disseminated encephalomyelitis (ADEM)-like demyelinating disease in the CNS and the other with subclinical peripheral neuropathy, were diagnosed by whole exome sequencing. 5 Our patient did not have peripheral neuropathy or hemolysis but inflammatory CNS lesions as sole and recurrent manifestation. After CNS infection was ruled out in the first two episodes, clinical and/or MRI findings were considered compatible with ADEM in two different tertiary referral centers.…”

Section: Discussionmentioning

confidence: 55%

“…Inflammatorydemyelinating lesions of middle cerebellar peduncles (as in the third attack of our patient) were also present in the four patients reported so far. 5 CD59 is known to shed from cell membranes by phospholipases and a soluble form is present in plasma. 14 So, until we provided and started eculizumab, we used FFP biweekly and did not observe any recurrence during the 3-month period.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Demyelinating Episodes as Sole Manifestation of Inherited CD59 Deficiency

et al. 2019

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Defects in the regulatory components of the complement system can lead to inflammatory diseases. We present a patient who had four episodes of demyelination in the central nervous system as the only manifestation of inherited CD59 deficiency. Relapsing encephalopathy partially responsive to intravenous immunoglobulin and steroid treatments on the background of parental consanguinity suggested an inherited immune dysregulation. Next generation sequencing revealed homozygous mutation in the CD59 gene, confirmed by lack of CD59 expression on flow cytometry. Inherited CD59 deficiency is a rare autosomal recessive condition characterized by chronic hemolysis, recurrent strokes, and relapsing peripheral demyelinating neuropathy mimicking Guillain–Barré syndrome or chronic inflammatory demyelinating polyneuropathy. Recurrent central nervous system demyelinating episodes as the only manifestation has not been reported to date in inherited CD59 deficiency. This entity should be considered in the differential diagnosis of patients with early-onset recurrent neurological diseases with central or peripheral origin.

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“…5 6 The spectrum of neurologic findings was further expanded with the reporting of Moyamoya syndrome, progressive stenosis of cerebral arteries with recurrent infarctions, acute-onset immune-mediated cerebellitis, hemorrhagic myelitis, acute disseminated encephalomyelitis-like demyelination, or recurrent demyelination in the central nervous system. 7 8 9 Acquired monocular abducens nerve palsy has not been previously described in CD59 deficiency. Our patient had isolated monocular abducens paralysis and a pontine lesion consistent with the clinical findings was detected on brain MRI.…”

Section: Discussionmentioning

confidence: 93%

Recurrent Blistering Skin Lesions and Reversible Monocular Abducens Paralysis in a Patient with CD59 Deficiency

et al. 2022

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Congenital CD59 deficiency is an autosomal recessive disease characterized by mild-to-moderate chronic intravascular hemolysis, relapsing demyelinating peripheral neuropathies, and recurrent ischemic central nervous system strokes. We report a 2-year-old Turkish girl with a history of two episodes of Guillain-Barré syndrome-like acute weakness, reversible monocular abducens paralysis, and recurrent blistering skin lesions during periods of upper respiratory tract infections. Reversible monocular abducens palsy and recurrent blistering skin lesions have not been reported previously in cases of congenital CD59 deficiency.

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Uncontrolled inflammation of the nervous system

Cited by 9 publications

References 8 publications

Astrocyte- and Neuron-Derived Extracellular Vesicles from Alzheimer’s Disease Patients Effect Complement-Mediated Neurotoxicity

Astrocyte- and Neuron-Derived Extracellular Vesicles from Alzheimer’s Disease Patients Effect Complement-Mediated Neurotoxicity

Recurrent Demyelinating Episodes as Sole Manifestation of Inherited CD59 Deficiency

Recurrent Blistering Skin Lesions and Reversible Monocular Abducens Paralysis in a Patient with CD59 Deficiency

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