Comprehensive Neural Antibody Testing Broadens the Diagnostic Spectrum of Autoimmune Neurological Disease in a Multi-ethnic Southeast Asian Cohort
Amy Quek1, Yihui Goh1, Derek Soon1, Wei Ping Kay Ng1, Raymond Seet2, Benjamin Ong1
1National University Hospital, 2National University of Singapore
Objective:

To describe temporal trends, positivity rates and antibody spectrum identified through neural antibody testing at a single tertiary academic centre in Singapore. 

Background:

Autoimmune encephalitis and paraneoplastic neurological disorders are treatable but readily missed when antibody testing is limited. In Southeast Asia, locally available commercial cell-based assays cover a narrow antibody subset, and the disease spectrum detectable through comprehensive panel testing has not been systematically described. 

Design/Methods:

Retrospective review of patients who underwent neural antibody testing at the National University Hospital, Singapore between 1 January 2018 and 31 December 2024. Patients included had standalone NMDAR cell-based assay (CBA) locally, and/or paraneoplastic (PNEO) and autoimmune encephalopathy (ENC) panels at the Mayo Clinic Neuroimmunology Laboratory. Patients tested only for AQP4 and MOG were excluded. 

Results:

Of 1465 patients tested, 925 met inclusion criteria (median age 51 years, IQR 17-67; 53% female; Chinese 67.9%, Malay 13.1%, Indian 7.5%, others 11.5%). A total of 2168 neural antibody tests were performed: 1278 panels (1125 ENC, 153 PNEO), and 890 CBAs (performed locally or via separate referral for NMDAR, glycine receptor, AQP4, MOG); 513 of 751 panel-tested patients (68%) had paired serum and CSF. Ninety patients (9.7%) had clinically significant seropositivity, spanning nineteen distinct neural antibodies. The most frequent were NMDAR (n=29), VGCC P/Q-type (n=15), GFAP (n=8), GABA-B (n=7), LGI1 (n=7) and high titre GAD65 (n=6); rarer antibodies included mGluR1, IgLON5, AP3B2, and AMPAR. Seventeen patients (18.9%) had two or more coexisting antibodies. 

Conclusions:

Comprehensive testing in this seven-year multi-ethnic Southeast Asian cohort identified a diverse neural antibody spectrum, including rarer antibodies undetectable by currently available commercial assays. These findings suggest the apparent rarity of certain antibody-mediated neurological disorders in this region may reflect limits of regional testing rather than true differences in disease frequency and support a broadened approach to antibody evaluation in patients with suspected autoimmune neurological disease.

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