Table 1:

Antibodies that may be found in autoimmune limbic encephalitis, and their tumour associations

Antibodies*Main tumour associationApproximate tumour frequency, %
Antibodies to extracellular cell surface or synaptic proteins
LGI112,14Various (thymoma, breast, thyroid, colon, pancreatic and other cancers)10
CASPR210,14Thymoma20
GABABR6,17SCLC50
AMPAR18,19SCLC, thymoma60
NMDAR20Ovarian teratoma40
mGluR521Hodgkin’s lymphoma50
Neurexin-3-α22None identifiedNA
Antibodies to intracellular proteins
Hu8,23SCLC> 90§
Ma224Testicular tumour> 90
GAD25SCLC, thymoma25**
Amphiphysin26SCLC, breast cancer> 90
CV2/CRMP527SCLC, thymoma> 90
AK528None identifiedNA
  • Note: AK5 = adenylate kinase 5, ALE = autoimmune limbic encephalitis, AMPAR = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, CASPR2 = contactin-associated protein-like 2, CRMP5 = collapsin response mediator protein 5, GABABR = γ-aminobutyric acid B receptor, GAD = glutamic acid decarboxylase, LGI-1 = leucine-rich glioma inactivated 1, mGluR5 = metabotropic glutamate receptor 5, NA = not applicable, NMDAR = N-methyl-d-aspartate receptor, SCLC = small-cell lung cancer.

  • * Antibodies in bold are major diagnostic considerations in patients with ALE.

  • Thymoma is more likely in patients with anti-CASPR2 antibodies and concomitant peripheral nervous system hyperexcitability, or dual anti-LGI1/CASPR2 antibody positivity.

  • Ovarian teratoma is most likely in female patients with anti-NMDAR antibodies, who are between the ages of 12 and 45 years. Tumours are less common in older patients with anti-NMDAR antibodies and are more likely to be carcinomas.

  • § SCLC is most likely in adults with anti-Hu antibodies. Tumours are less common in children with anti-Hu antibodies and more likely to be neuroblastomas.

  • Testicular tumour is most likely in young (< 45 yr) male patients with anti-Ma2 antibodies. In older patients with co-existent anti-Ma1 antibodies, a variety of other tumours have been identified, most commonly non-SCLC.

  • ** Likelihood of tumour is higher in older (median age 60 yr) patients with anti-GAD antibodies or who have co-existent neuronal cell-surface antibodies (e.g., anti-GABABR antibodies).