The expanded clinical spectrum of anti-GABABR encephalitis and added value of KCTD16 autoantibodies

Brain. 2019 Jun 1;142(6):1631-1643. doi: 10.1093/brain/awz094.


In this study we report the clinical features of 32 patients with gamma aminobutyric acid B receptor (GABABR) antibodies, identify additional autoantibodies in patients with anti-GABABR encephalitis that mark the presence of an underlying small cell lung carcinoma and optimize laboratory methods for the detection of GABABR antibodies. Patients (n = 3225) were tested for the presence of GABABR antibodies using cell-based assay, immunohistochemistry and live hippocampal neurons. Clinical data were obtained retrospectively. Potassium channel tetramerization domain-containing (KCTD)16 antibodies were identified by immunoprecipitation, mass spectrometry analysis and cell-based assays. KCTD16 antibodies were identified in 23/32 patients with anti-GABABR encephalitis, and in 1/26 patients with small cell lung carcinoma and Hu antibodies, but not in 329 healthy subjects and disease controls. Of the anti-GABABR encephalitis patients that were screened sufficiently, 18/19 (95%) patients with KCTD16 antibodies had a tumour versus 3/9 (33%) anti-GABABR encephalitis patients without KCTD16 antibodies (P = 0.001). In most cases this was a small cell lung carcinoma. Patients had cognitive or behavioural changes (97%) and prominent seizures (90%). Thirteen patients developed a refractory status epilepticus with intensive care unit admittance (42%). Strikingly, 4/32 patients had a rapidly progressive dementia. The addition of KCTD16 to the GABABR cell-based assay improved sensitivity of the in-house fixed cell-based assay, without loss of specificity. Twenty-two of 26 patients improved (partially) to immunotherapy or chemotherapy. Anti-GABABR encephalitis is a limbic encephalitis with prominent, severe seizures, but patients can also present with rapidly progressive dementia. The co-occurrence of KCTD16 antibodies points towards a paraneoplastic origin. The addition of KCTD16 improves the sensitivity of the cell-based assay.

Keywords: antineuronal autoantibodies; autoimmune encephalitis; neuronal surface antigens; paraneoplastic neurological disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / immunology*
  • Encephalitis / diagnosis*
  • Encephalitis / genetics*
  • Female
  • Humans
  • Immunologic Factors
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology
  • Neurons / pathology
  • Seizures / diagnosis
  • Seizures / genetics
  • Status Epilepticus / genetics
  • Status Epilepticus / immunology
  • gamma-Aminobutyric Acid / genetics
  • gamma-Aminobutyric Acid / immunology*


  • Autoantibodies
  • Immunologic Factors
  • Intracellular Signaling Peptides and Proteins
  • KCTD16 protein, human
  • Nerve Tissue Proteins
  • gamma-Aminobutyric Acid