Table 2.
Demographic and clinical characteristics of the main CNS autoantibodies targeting intracellular antigens associated with cognitive impairment/encephalopathy according to the largest series reported.
| Intracellular target | Female sex (%) | Typical age of onset | Cognitive impairment (%) | Common clinical accompaniments | Cancer risk (cancer types) |
|---|---|---|---|---|---|
| AK5113 | 30 | 60–70 | 100 | LE | 0% |
| Amphiphysin114 | 60 | 60–70 | 30 | Encephalopathy; peripheral neuropathy; myelitis; SPS | 80% (breast, small cell lung) |
| ANNA-1 (Hu)115,116 | 55–65 | 60–70 | 10–20 | LE; sensory neuronopathy; autoimmune GI dysmotility | 85–90% (small cell lung) |
| ANNA-2 (Ri)39 | 65 | 60–70 | 10–20 | Brainstem symptoms; opsoclonus-myoclonus; laryngospasm; jaw opening dystonia; ataxia | 75% (small cell lung, breast) |
| ANNA-3117 | 50–60 | 50–60 | 10–20 | Limbic encephalitis; cerebellar ataxia; peripheral neuropathy; myelopathy | 80–90% (small cell lung) |
| CRMP5 (CV2)118,119 | 30–60 | 60–70 | 40 | Chorea; optic neuropathy/retinopathy; peripheral neuropathy; myelitis | 90% (small cell lung, thymoma) |
| GAD-65120,121 | 75–85 | 50–60 | 3–5 | LE; SPS; ataxia; seizures | 8% (small cell lung) |
| GFAP42 | 68 | 50–60 | 15–60 | Meningo-encephalo-myelitis or limited forms; optic disc edema; tremor; viral-like prodrome | 35% (teratoma) |
| ITPR1122 | 70 | 60–70 | 21 | Cerebellar ataxia; peripheral neuropathy; encephalitis with seizures; myelopathy | 30–40% (breast cancer) |
| Kelch11123 | 0 | 40–50 | 5–10 | Ataxia; brainstem dysfunction with hearing loss; encephalopathy | 100% (testicular seminoma) |
| Ma2 (Ta)45 | 32 | 60–70 | 68 | LE; diencephalic syndrome (narcolepsy/cataplexy); brainstem symptoms | 90% (testicular tumors) |
| NfL124 | 50 | 60–70 | 33 | Ataxia; encephalopathy; myelitis | 76% [neuroendocrine (small cell lung, Merkel cell)] |
| PCA-2/MAP1B125 | 70 | 60–70 | 30 | Ataxia; brainstem symptoms; peripheral neuropathy | 90% (small cell lung) |
AK5, adenylate kinase 5; ANNA-1/2, anti-neuronal nuclear antibodies type-1/2; CNS, central nervous system; CRMP5, collapsin response-mediator protein-5; GAD-65, glutamic acid decarboxylase-65; GFAP, glial fibrillary acidic protein; GI, gastrointestinal; LE, limbic encephalitis; NfL, neurofilament light chain; PCA-2/MAP1B, Purkinje cells antigens-2/microtubule-associated protein 1B; SPS, stiff-person syndrome. (Modified with permission from Table 2 in in ref.75).