Cerebrospinal Fluid GAD65 ‐Antibody Levels Accurately Identify Relevant Neurological Diseases

Retrospective cohort study to investigate which factors most reliably distinguish incidental GAD65-antibodies (iGAD65) from true GAD65-antibody neurological disease (tGAD65). 167 adults with positive serum and CSF GAD65-antibodies (> 0.02 nmol/L by radioimmunoassay) were classified as tGAD65 or iGAD65, with diagnostic performance of paraclinical parameters compared in discovery and validation cohorts. CSF GAD65-antibody titers ≥ 1 nmol/L performed best in discovery (AUC 0.956) and validation (AUC 0.949; p = 0.814), with 89.7% sensitivity and 94% specificity for identifying tGAD65. Serum titers > 20 nmol/L and indices of intrathecal synthesis showed lower discriminative ability. Our finding aims to reduce misdiagnosis and identify potential immunotherapy-responsive diseases.

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Publication Details

Journal
Annals of Clinical and Translational Neurology
Published
2026-11-03
DOI
https://doi.org/10.1002/acn3.70578
Primary Topic
Autoimmune Neurological Disorders and Treatments
Type
article
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article

Cerebrospinal Fluid GAD65 ‐Antibody Levels Accurately Identify Relevant Neurological Diseases

Max Charles Herman, Eric Newman, Alfonso Sebastian Lopez-Chiriboga, Sarosh R. Irani et al.
Annals of Clinical and Translational Neurology
Autoimmune Neurological Disorders and Treatments
article

Cerebrospinal Fluid GAD65 ‐Antibody Levels Accurately Identify Relevant Neurological Diseases

Max Charles Herman, Eric Newman, Alfonso Sebastian Lopez-Chiriboga, Sarosh R. Irani, Zoaib Habib Tharwani, Andrew B. McKeon, Yoav D. Piura, Gregory Scott Day, Snigdha Kotaru, Maya Marzello
article en

Abstract

Retrospective cohort study to investigate which factors most reliably distinguish incidental GAD65-antibodies (iGAD65) from true GAD65-antibody neurological disease (tGAD65). 167 adults with positive serum and CSF GAD65-antibodies (> 0.02 nmol/L by radioimmunoassay) were classified as tGAD65 or iGAD65, with diagnostic performance of paraclinical parameters compared in discovery and validation cohorts. CSF GAD65-antibody titers ≥ 1 nmol/L performed best in discovery (AUC 0.956) and validation (AUC 0.949; p = 0.814), with 89.7% sensitivity and 94% specificity for identifying tGAD65. Serum titers > 20 nmol/L and indices of intrathecal synthesis showed lower discriminative ability. Our finding aims to reduce misdiagnosis and identify potential immunotherapy-responsive diseases.

Annals of Clinical and Translational Neurology
St. Luke's University Health Network (US), Mayo Clinic (US), University of Oxford (GB), Mayo Clinic in Florida (US)
Openalex Percentile: Top 16%
Autoimmune Neurological Disorders and Treatments
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Cerebrospinal Fluid GAD65 ‐Antibody Levels Accurately Identify Relevant Neurological Diseases — Max Charles Herman, Eric Newman, et al. · Annals of Clinical and Translational Neurology (2026) | TGRS Research Map | TGRS