Comparisons of autoantibodies against LGI1, CASPR2, and the double-negative VGKC antibodies
| Evidence | Autoantibody | |||
|---|---|---|---|---|
| LGI1 | CASPR2 | Double-negative VGKC | ||
| Clinical features | Well-delineated clinical syndromes? | Yes24 25: Faciobrachial dystonic seizures; Limbic encephalitis (other frequent focal seizure semiologies, encephalopathy, sleep disorder, amnesia, anxiety, emotionality dysautonomia); Hyponatraemia in ~65% More rarely, neuromyotonia and Morvan’s syndrome | Yes8 9 23: CNS: limbic encephalitis—seizures, confusion, hallucinations, insomnia PNS: neuromyotonia (neuropathic pain, spasms, cramps) Morvan’s syndrome: above including insomnia and dysautonomia, often with weight loss | No: 5% rate in healthy controls and detected in heterogeneous, often non-immune, syndromes including varied epilepsies; widespread, non-neuropathic pain; Parkinson’s disease; headache; primary psychiatric conditions26– 28 32 |
| Demographics: gender ratio and median age of onset | M (2:1) 60–70 years25 | M (8:1) 50–60 years | No known predilection (M:F 1:1; 18–85 years with no peak onset age26 28 32) | |
| Immunotherapy-responsive (%) | Highly: 100%26 96%24 97%25 29 78%9 | Highly: 100%37 86%26 | Limited, and likely accounted for by referral bias and/or placebo effect: 27%28 46%26 | |
| Serological | Epitope | Extracellular (both receptor docking and non-docking domains of this secreted protein;8 21 28) | Extracellular domain8 9 28 | Intracellular aspects (including Kv1 channels), and non-mammalian targets28 |
| Rate in healthy controls | <1%38 | <1%38 | ~5%,2 6 28 39 | |
| Other associations/markers | Rarely thymoma <5% | Thymoma 20-50%, especially those with Morvan’s syndrome and neuromyotonia | Possibly malignancies33– 36 | |
| Genetic | HLA associations | HLA-DRB1*07:01 (~95%)26 32 40 41 | HLA-DRB1*11:01 (~50%)32 | Nil32 |
| Evidence of pathogenicity | In vitro and in vivo | Functional blocking of LGI1-ADAM22 interactions21 42
Internalisation21 25 LGI1 IgGs and monoclonal antibodies induce memory deficits in vivo20 21 | Internalisation noted in some studies; pain reproduced in experimental animals43 | Nil |
ADAM, a disintegrin and metalloprotease; CASPR2, contactin-associated protein like-2; CNS, central nervous system; F, female; HLA, human leukocyte antigen; LGI1, leucine-rich glioma-inactivated 1; M, male; PNS, peripheral nervous system; VGKC, voltage-gated potassium channel.