Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome

J Neurol. 2020 Jul;267(7):2101-2114. doi: 10.1007/s00415-020-09814-3. Epub 2020 Apr 3.


Objective: To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods: Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results: Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6-46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions: This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

Keywords: Autoimmune encephalitis; Immunotherapy; Laboratory test evaluation; Neural autoantibodies; Outcome.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies* / analysis
  • Autoantibodies* / blood
  • Autoantibodies* / cerebrospinal fluid
  • Autoimmune Diseases of the Nervous System / blood
  • Autoimmune Diseases of the Nervous System / cerebrospinal fluid
  • Autoimmune Diseases of the Nervous System / diagnosis*
  • Autoimmune Diseases of the Nervous System / immunology
  • Child
  • Child, Preschool
  • Diagnostic Techniques, Neurological / standards*
  • Female
  • Glutamate Decarboxylase / immunology*
  • HEK293 Cells
  • Humans
  • Immunologic Tests / standards*
  • Infant
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Male
  • Membrane Proteins / immunology*
  • Mental Disorders / blood
  • Mental Disorders / cerebrospinal fluid
  • Mental Disorders / diagnosis*
  • Mental Disorders / immunology
  • Middle Aged
  • Nerve Tissue Proteins / immunology*
  • Neuropil / immunology*
  • Potassium Channels, Voltage-Gated / immunology*
  • Receptors, AMPA / immunology*
  • Receptors, GABA-B / immunology*
  • Receptors, Glycine / immunology*
  • Receptors, N-Methyl-D-Aspartate / immunology*
  • Reproducibility of Results
  • Retrospective Studies
  • Young Adult


  • Autoantibodies
  • CNTNAP2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • LGI1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Potassium Channels, Voltage-Gated
  • Receptors, AMPA
  • Receptors, GABA-B
  • Receptors, Glycine
  • Receptors, N-Methyl-D-Aspartate
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2