Antibodies to neuronal surface antigens in patients with a clinical diagnosis of neurodegenerative disorder

• Published in: Brain, behavior, and immunity behavior, and immunity, 2021-08, Vol.96, p.106-112
• Main Authors: Giannoccaro, Maria Pia, Gastaldi, Matteo, Rizzo, Giovanni, Jacobson, Leslie, Vacchiano, Veria, Perini, Giulia, Capellari, Sabina, Franciotta, Diego, Costa, Alfredo, Liguori, Rocco, Vincent, Angela
• Format: Article
• Language: English
• Subjects: Autoimmune dementia; Autoimmune encephalitis; Neurodegenerative disorders; Neuronal surface antibodies
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2021.05.017

•Neuronal surface antibodies are relatively frequent in patients with neurodegenerative disorders.•An unclassified diagnosis and an irregular progression predicted seropositivity.•Seropositivity was associated with ataxia, reflex myoclonus and sleep disorders.•Less than a half of seropositive cases met a priori the current criteria for autoimmune encephalitis.•There may be a proportion of cases of neurodegenerative diseases who could respond to immunotherapies. Autoimmune encephalitis due to antibodies against neuronal surface antigens (NSA-Ab) frequently presents with cognitive impairment, often as the first and prevalent manifestation, but few studies have systematically assessed the frequency of NSA-Ab in consecutive patients with established neurodegenerative disorders. We studied sera of 93 patients (41F, 52 M), aged 69.2 ± 9.4 years, with neurodegenerative conditions, and of 50 population controls aged over 60 years. Specific NSA-Abs were investigated by antigen-specific cell-based assays (CBAs). After testing, we evaluated the association between the NSA-Abs and clinical, CSF and radiological features. The patients included 13/93 (13.8%) who had specific antibodies to neuronal surface antigens: 6 GlyR, 3 GABAAR (1 also positive for AMPAR), 2 LGI1, 1 CASPR2 and 1 GABABR. One of the 50 controls (2%) was positive for NMDAR antibody and the others were negative on all tests (P = 0.020). No difference was observed in antibody frequency between patients presenting with parkinsonism and those presenting with dementia (P = 0.55); however, NSA-Ab were more frequent in those with unclassified forms of dementia (5/13, 38.5%) than in those with unclassified parkinsonism (2/9, 22.2%) or with classified forms of dementia (4/43, 9.3%) or parkinsonism (2/28, 7.1%) (P = 0.03). A logistic regression analysis demonstrated that an unclassified diagnosis (P = 0.02) and an irregular progression (P = 0.024) were predictors of seropositive status. NSA-Abs are relatively frequent in patients with neurodegenerative disorders, particularly in those with an irregular disease progression of atypical clinical features, inconsistent with a recognized diagnosis. The significance of these antibodies and their possible primary or secondary roles need to be investigated in prospective studies.