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Neurology : Neuroimmunology & Neuroinflammation 6(5), e603 (2019). doi:10.1212/NXI.0000000000000603, Published by Lippincott Williams & Wilkins, Philadelphia, Pa.

Immunoglobulin G (IgG) autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG) have recently been associated with autoimmune CNS demyelination. We present the case of a 35-year-old patient who was seronegative for MOG-IgG (as confirmed by means of three independent immunoassays) during two corticosteroid-responsive attacks of brainstem encephalitis and optic neuritis, respectively, but turned positive for MOG-IgG under treatment with interferon-beta (IFN-beta), which was commenced 6 months after onset of the first attack. MOG-IgG serum levels declined after therapy was switched to glatiramer acetate. The fact that seroconversion was first observed under treatment with IFN-beta is in accordance with previous evidence suggesting a role of IFN-beta in disease exacerbation in antibody-mediated disorders.

Objective To study the prevalence of autoantibodies to synapsin in patients with psychiatric and neurological disorders and to describe clinical findings in synapsin antibody positive patients. Methods Sera of 375 patients with different psychiatric and neurological disorders and sera of 97 healthy controls were screened (dilution 1:320) for anti-synapsin IgG using HEK293 cells transfected with rat synapsin Ia. Positive sera were further analyzed by immunoblots with brain tissue from wild type and synapsin knock out mice and with HEK293 cells transfected with human synapsin Ia and Ib. Binding of synapsin IgG positive sera to primary neurons was studied using murine hippocampal neurons. Results IgG in serum from 23 (6.1%) of 375 patients, but from none of the 97 healthy controls (p = 0.007), bound to rat synapsin Ia transfected cells with a median (range) titer of 1:1000 (1:320–1:100,000). Twelve of the 23 positive sera reacted with a protein of the molecular size of synapsin I in immunoblots of wild type but not of synapsin knock out mouse brain tissue. Out of 19/23 positive sera available for testing, 13 bound to human synapsin Ia and 16 to human synapsin Ib transfected cells. Synapsin IgG positive sera stained fixed and permeabilized murine hippocampal neurons. Synapsin IgG positive patients had various psychiatric and neurological disorders. Tumors were documented in 2 patients (melanoma, small cell lung carcinoma); concomitant anti-neuronal or other autoantibodies were present in 8 patients. Conclusions Autoantibodies to human synapsin Ia and Ib are detectable in a proportion of sera from patients with different psychiatric and neurological disorders, warranting further investigation into the potential pathophysiological relevance of these antibodies.

Biomarkers are required for the diagnosis and monitoring of disease progression in Parkinson disease (PD). To date, most studies have concentrated on α-synuclein (α-Syn), a protein involved in Parkinson disease pathogenesis, as a potential biomarker, with inconsistent outcomes. Recently, naturally occurring autoantibodies against α-Syn (α-Syn-nAbs) have been detected in the serum of patients with PD. They represent a putative diagnostic marker for PD.We established and validated an ELISA to quantify α-Syn-nAbs in serum samples. We analyzed serum samples from 62 patients with PD, 46 healthy controls (HC), and 42 patients with Alzheimer disease (AD) using this newly established ELISA. Additionally, serum levels of endogenous α-Syn were measured.There was a significant difference in α-Syn-nAbs levels between the investigated groups (p = 0.005; Kruskal-Wallis test). Levels of α-Syn-nAbs were significantly lower in patients with PD compared to HC (p0.05; Dunn multiple comparison post hoc test) or patients with AD (p0.05). Furthermore, we detected no difference between patients with AD and HC. The sensitivity and specificity of the assay for patients with PD vs. HC were 85% and 25%, respectively. The α-Syn-nAbs levels did not correlate with age, HoehnYahr status, or duration of disease. Endogenous α-Syn had no influence on α-Syn-nAbs levels in sera.Using a well-validated assay, we detected reduced α-Syn-nAbs levels in patients with PD compared to patients with AD and HC. The assay did not achieve criteria for use as a diagnostic tool to reliably distinguish PD from HC. Further studies are needed to assess α-Syn-nAbs as a biomarker in PD.

In 1982, Dr. Ian Carr described personality changes and memory loss in his 15-year-old daughter, who had limbic encephalitis and Hodgkin lymphoma (HL).1 He assumed “a circulating neurotransmitter-like molecule produced by the neoplasm” causing the brain disease, and noted that it “may be reversible and can be remembered as the Ophelia syndrome.” Almost 30 years later, Lancaster et al.2 identified antibodies against the metabotropic glutamate receptor 5 (mGluR5) as Carr's neurotransmitter-like molecule in 2 patients with limbic encephalitis and HL. Encephalitis was reversible in both patients receiving tumor treatment. The clinical spectrum is largely unknown and the role of immunotherapy is unclear.