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. 2021 Aug:96:106-112.
doi: 10.1016/j.bbi.2021.05.017. Epub 2021 May 20.

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

Maria Pia Giannoccaro  1 , Matteo Gastaldi  2 , Giovanni Rizzo  3 , Leslie Jacobson  4 , Veria Vacchiano  5 , Giulia Perini  6 , Sabina Capellari  5 , Diego Franciotta  6 , Alfredo Costa  7 , Rocco Liguori  5 , Angela Vincent  8
Affiliations

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

Maria Pia Giannoccaro et al. Brain Behav Immun. 2021 Aug.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Autoimmune dementia; Autoimmune encephalitis; Neurodegenerative disorders; Neuronal surface antibodies.

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