Data from: Paraneoplastic neuronal intermediate filament autoimmunity

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 alpha
internexin, neurofilament light [NF-L], medium, or heavy chain, and
peripherin). NIF-IgGs were correlated with neurological 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 NF-L-IgG (21
patients, who mostly had ≥4 NIF-IgGs detected) or its absence (44
patients, who mostly had ≤2 NIF-IgGs detected). Among NF-L-IgG positive
patients, 19/21 had ≥1 subacute onset CNS disorders: cerebellar ataxia
(11), encephalopathy (11); 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 NF-L-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 NF-L-IgG, defines a
paraneoplastic CNS disorder (usually ataxia or encephalopathy)
accompanying neuroendocrine lineage neoplasia.