Identification of Leiomodin-1 Autoantibody as a Novel Biomarker in Cryptogenic New-onset Refractory Status Epilepticus
Soo Jean Shin1, Soo Hyun Ahn1, Yoonhyuk Jang1, Andrew Knight2, Silvana De Lorenzo2, Surendra Dasari2, Su Yee Mon1, Yoon Hee Shin1, Yihui Goh3, Kon Chu1, Sang Kun Lee1, Divyanshu Dubey2, Soon-Tae Lee1
1Neurology, Seoul National University Hospital, 2Neurology, Mayo Clinic, 3Neurology, National University of Singapore
Objective:
To identify potential biomarkers in cryptogenic new-onset refractory status epilepticus (C-NORSE) by discovering autoantibodies that mediate disease pathogenesis.
Background:
While C-NORSE is mediated by inflammatory responses, reliable serologic biomarkers for predicting functional outcomes remain lacking. Phage immunoprecipitation sequencing (PhIP-seq) enables the discovery of novel antibodies that may aid disease stratification and prognostication.
Design/Methods:
Cerebrospinal fluid (CSF) from patients enrolled in a multicenter C-NORSE cohort were analyzed using PhIP-seq. Enzyme-linked immunosorbent assay (ELISA) was used to validate and screen for LMOD1-IgG in serum and CSF of C-NORSE and other neurologic diseases. Clinical outcomes, including modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune encephalitis (CASE), were evaluated over two years.
Results:
PhIP-seq was performed in 26 C-NORSE CSF. Among the top hits, leiomodin-1 (LMOD1) was selected as the leading autoantigen based on its prognostic potential in the development set, CNS expression, and prior reports of antibody relevance. The optical density cutoff for LMOD1-IgG ELISA was determined as 0.30 based on receiver operating characteristic analysis. The diagnostic performance of CSF testing exceeded that of serum. Using this cutoff, a total of 266 CSF were screened for LMOD1-IgG (C-NORSE=57, other autoimmune neurologic diseases=104, other non-autoimmune neurological diseases=105). LMOD1-IgG was detected in 16.5% (44/266) of samples, indicating that the antibody is not specific to C-NORSE. However, LMOD1-IgG-positivity was strongly associated with poor prognosis in C-NORSE. One-year and 2-year mRS and CASE scores were significantly worse in the LMOD1-positive compared to the LMOD1-negative patients (all P<0.05). While LMOD1-negative showed gradual improvement, none of the LMOD1-positive patients achieved mRS≤2 during the two-year follow-up. In addition, the median duration of continuous intravenous anesthesia and unconsciousness were significantly longer in the LMOD1-positive group.
Conclusions:
LMOD-IgG was associated with significantly worse outcomes in C-NORSE. The presence of the antibody may identify a vulnerable subgroup predisposed to severe disease and NORSE-related brain injury.
Generative AI Usage
No, did not use generative AI in the drafting or editing in this abstract.
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