TY - JOUR
T1 - Paraneoplastic neuronal intermediate filament autoimmunity
AU - Basal, Eati
AU - Zalewski, Nicholas
AU - Kryzer, Thomas J.
AU - Hinson, Shannon R.
AU - Guo, Yong
AU - Dubey, Divyanshu
AU - Benarroch, Eduardo E.
AU - Lucchinetti, Claudia F.
AU - Pittock, Sean J.
AU - Lennon, Vanda A.
AU - McKeon, Andrew
N1 - Funding Information:
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was funded by Mayo Clinic.
Funding Information:
E. Basal and N. Zalewski report no disclosures relevant to the manuscript. T. Kryzer is named inventor on a patent relating to AQP4 and MAP1B antibodies as markers of autoimmune neurologic disease. S. Hinson, Y. Guo, D. Dubey, and E. Benarroch report no disclosures relevant to the manuscript. C. Lucchinetti has received funding support from Biogen, Novartis, and Mallinkrodt and shares in royalties from marketing kits for detecting AQP4 autoantibody. S. Pittock holds patents that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker; has patents pending for MAP1B-IgG and Septin-5-IgG as markers of neurologic autoimmunity and paraneoplastic disorders; consulted for Alexion and Medimmune; and received research support
Publisher Copyright:
© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2018
Y1 - 2018
N2 - Objective To describe paraneoplastic neuronal intermediate filament (NIF) autoimmunity. Methods Archived patient and control serum and CSF specimens were evaluated by tissue-based indirect immunofluorescence assay (IFA). Autoantigens were identified by Western blot and mass spectrometry. NIF specificity was confirmed by dual tissue section staining and 5 recombinant NIF-specific HEK293 cell-based assays (CBAs, for α-internexin, neurofilament light [NfL], neurofilament medium, or neurofilament heavy chain, and peripherin). NIF-immunoglobulin Gs (IgGs) were correlated with neurologic syndromes and cancers. Results Among 65 patients, NIF-IgG-positive by IFA and CBAs, 33 were female (51%). Median symptom onset age was 62 years (range 18-88). Patients fell into 2 groups, defined by the presence of NfL-IgG (21 patients, who mostly had ≥4 NIF-IgGs detected) or its absence (44 patients, who mostly had ≤2 NIF-IgGs detected). Among NfL-IgG-positive patients, 19/21 had ≥1 subacute onset CNS disorders: cerebellar ataxia (11), encephalopathy (11), or myelopathy (2). Cancers were detected in 16 of 21 patients (77%): carcinomas of neuroendocrine lineage (10) being most common (small cell [5], Merkel cell [3], other neuroendocrine [2]). Two of 257 controls (0.8%, both with small cell carcinoma) were positive by both IFA and CBA. Five of 7 patients with immunotherapy data improved. By comparison, the 44 NfL-IgG-negative patients had findings of unclear significance: diverse nervous system disorders (p = 0.006), as well as limited (p = 0.003) and more diverse (p < 0.0001) cancer accompaniments. Conclusions NIF-IgG detection by IFA, with confirmatory CBA testing that yields a profile including NfL-IgG, defines a paraneoplastic CNS disorder (usually ataxia or encephalopathy) accompanying neuroendocrine lineage neoplasia.
AB - Objective To describe paraneoplastic neuronal intermediate filament (NIF) autoimmunity. Methods Archived patient and control serum and CSF specimens were evaluated by tissue-based indirect immunofluorescence assay (IFA). Autoantigens were identified by Western blot and mass spectrometry. NIF specificity was confirmed by dual tissue section staining and 5 recombinant NIF-specific HEK293 cell-based assays (CBAs, for α-internexin, neurofilament light [NfL], neurofilament medium, or neurofilament heavy chain, and peripherin). NIF-immunoglobulin Gs (IgGs) were correlated with neurologic syndromes and cancers. Results Among 65 patients, NIF-IgG-positive by IFA and CBAs, 33 were female (51%). Median symptom onset age was 62 years (range 18-88). Patients fell into 2 groups, defined by the presence of NfL-IgG (21 patients, who mostly had ≥4 NIF-IgGs detected) or its absence (44 patients, who mostly had ≤2 NIF-IgGs detected). Among NfL-IgG-positive patients, 19/21 had ≥1 subacute onset CNS disorders: cerebellar ataxia (11), encephalopathy (11), or myelopathy (2). Cancers were detected in 16 of 21 patients (77%): carcinomas of neuroendocrine lineage (10) being most common (small cell [5], Merkel cell [3], other neuroendocrine [2]). Two of 257 controls (0.8%, both with small cell carcinoma) were positive by both IFA and CBA. Five of 7 patients with immunotherapy data improved. By comparison, the 44 NfL-IgG-negative patients had findings of unclear significance: diverse nervous system disorders (p = 0.006), as well as limited (p = 0.003) and more diverse (p < 0.0001) cancer accompaniments. Conclusions NIF-IgG detection by IFA, with confirmatory CBA testing that yields a profile including NfL-IgG, defines a paraneoplastic CNS disorder (usually ataxia or encephalopathy) accompanying neuroendocrine lineage neoplasia.
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U2 - 10.1212/WNL.0000000000006435
DO - 10.1212/WNL.0000000000006435
M3 - Article
C2 - 30282771
AN - SCOPUS:85055612700
VL - 91
SP - E1677-E1689
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 18
ER -