Publications

Authors:

Mckeon, Andrew; Shelly, Shahar; Zivelonghi, Cecilia; Basal, Eati; Dubey, Divyanshu; Flanagan, Eoin; Madhavan, Ajay A; Mariotto, Sara; Toledano, Michel; Tracy, Jennifer A; Zekeridou, Anastasia; Pittock, Sean J

Title:

Neuronal intermediate filament IgGs in CSF: Autoimmune Axonopathy Biomarkers

Year:

2021

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

A Stampa

Referee:

Sì

Name of journal:

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY

ISSN of journal:

2328-9503

N° Volume:

8

Number or Folder:

2

Page numbers:

425-439

Keyword:

Neurological autoimmunity; CSF-detected NIF-IgGs; neuronal intermediate filament; autoimmune axonopathy; biomarkers

Short description of contents:

Objectives: To describe CSF-defined neuronal intermediate filament (NIF) autoimmunity. Methods: NIF-IgG CSF-positive patients (41, 0.03% of 118599 tested, 1996-2019) were included (serum was neither sensitive nor specific). Criteria-based patient NIF-IgG staining of brain and myenteric NIFs was detected by indirect immunofluorescence assay (IFA); NIF-specificity was confirmed by cell-based assays (CBAs, alpha internexin, neurofilament light [NF-L]), heavy-[NF-H] chain). Results: Sixty-one percent of 41 patients were men, median age, 61 years (range, 21-88). Syndromes were encephalopathy predominant (23), cerebellar ataxia predominant (11), or myeloradiculoneuropathies (7). MRI abnormalities (T2 hyperintensities of brain, spinal cord white matter tracts. and peripheral nerve axons) and neurophysiologic testing (EEG, EMG, evoked potentials) co-localized with clinical neurological phenotypes (multifocal in 29%). Thirty patients (73%) had ≥ 1 immunological perturbation: cancer (paraneoplastic), 22; systemic infection (parainfectious [including ehrlichosis, 3] or HIV), 7; checkpoint-inhibitor cancer immunotherapy, 4; other, 5. Cancers were as follows: neuroendocrine-lineage carcinomas, 12 (small cell, 6; Merkel cell, 5; pancreatic, 1 [11/12 had NF-L-IgG detected, versus 8/29 others, P = 0.0005]) and other, 11. Onset was predominantly subacute (92%) and accompanied by inflammatory CSF (75%), and immunotherapy response (77%). In contrast, CSF controls (15684 total) demonstrated NIF-IgG negativity (100% of test validation controls), and low frequencies of autoimmune diagnoses (20% of consecutively referred clinical specimens) and neuroendocrine-lineage carcinoma diagnosis (3.1% vs. 30% of NIF cases), P < 0.0001. Median NF-L protein concentration was higher in 8 NF-L-IgG-positive patients (median, 6718 ng/L) than 16 controls. Interpretation: Neurological autoimmunity, defined by CSF-detected NIF-IgGs, represents a continuum of treatable axonopathies, sometimes paraneoplastic or parainfectious.

Web page:

https://doi.org/10.1002/acn3.51284

Product ID:

118709

Handle IRIS:

11562/1033385

Last Modified:

November 8, 2022

Bibliographic citation:

Mckeon, Andrew; Shelly, Shahar; Zivelonghi, Cecilia; Basal, Eati; Dubey, Divyanshu; Flanagan, Eoin; Madhavan, Ajay A; Mariotto, Sara; Toledano, Michel; Tracy, Jennifer A; Zekeridou, Anastasia; Pittock, Sean J, Neuronal intermediate filament IgGs in CSF: Autoimmune Axonopathy Biomarkers «ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY» , vol. 8 , n. 2 , 2021 , pp. 425-439

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