| Antibody/target | Antigen location | Typical syndrome/notes | Common tumor associations and approximate positivity rates if provided | Key mechanistic effect | Key evidence type | Primary sources |
|---|---|---|---|---|---|---|
| **LGI1** | Cell-surface/synaptic VGKC-complex–associated protein | Classic autoimmune **limbic encephalitis**; prominent seizures, memory impairment, psychiatric/behavioral change; **faciobrachial dystonic seizures (FBDS)** are highly specific; hyponatremia common (pqac-00000001, pqac-00000030) | Thymoma reported; approximate tumor positivity **5–10%** in Graus table (pqac-00000007) | Predominantly IgG4-mediated **disruption of LGI1–ADAM22/ADAM23 interactions**; reduction of synaptic **AMPAR** and Kv1 channel clusters; impaired LTP; increased excitability; some models suggest BBB tight-junction breakdown and possible complement/inflammatory effects (pqac-00000032, pqac-00000035, pqac-00000037) | Human clinical cohorts + in vitro/in vivo mechanistic models | Graus 2016, doi: https://doi.org/10.1016/S1474-4422(15)00401-9; Li 2021, doi: https://doi.org/10.3389/fneur.2021.674368; Ryding 2023, doi: https://doi.org/10.3390/cells13010015 (pqac-00000001, pqac-00000030, pqac-00000032) |
| **CASPR2** | Cell-surface/paranodal-synaptic protein | Limbic encephalitis spectrum with seizures/cognitive symptoms; can overlap with Morvan syndrome; relevant limbic involvement in autoimmune encephalitis panels (pqac-00000007, pqac-00000026) | Thymoma reported; approximate tumor positivity **20–50%** in Graus table (pqac-00000007) | **Disruption of CASPR2–contactin-2 interactions** and/or CASPR2 internalization; altered Kv1.2 surface expression, neuronal hyperexcitability, reduced AMPAR currents/LTP, memory impairment; glial activation and increased complement C3 in models (pqac-00000032, pqac-00000033, pqac-00000035) | Human clinical cohorts + in vitro/in vivo mechanistic models | Graus 2016, doi: https://doi.org/10.1016/S1474-4422(15)00401-9; Rada 2024, doi: https://doi.org/10.1212/NXI.0000000000200225; Ryding 2023, doi: https://doi.org/10.3390/cells13010015 (pqac-00000007, pqac-00000026, pqac-00000033) |
| **GABA<sub>B</sub>R** | Cell-surface/synaptic receptor | Autoimmune limbic encephalitis with **early and prominent seizures**; often included among core limbic AE antibodies (pqac-00000007, pqac-00000026) | **Small-cell lung carcinoma** common; approximate tumor positivity **~50%** in Graus table (pqac-00000007) | Evidence supports **direct inhibition/signaling blockade of receptor function** rather than major receptor-expression loss (pqac-00000038) | Human clinical association + mechanistic in vitro evidence/review synthesis | Graus 2016, doi: https://doi.org/10.1016/S1474-4422(15)00401-9; Rada 2024, doi: https://doi.org/10.1212/NXI.0000000000200225; Ryding 2023, doi: https://doi.org/10.3390/cells13010015 (pqac-00000007, pqac-00000026, pqac-00000038) |
| **AMPAR** | Cell-surface/synaptic glutamate receptor | Limbic encephalitis with memory disturbance, seizures, psychiatric symptoms; important cell-surface limbic AE subtype (pqac-00000007) | Thymoma and **small-cell lung cancer** reported; approximate tumor positivity **~65%** in Graus table (pqac-00000007) | **Receptor internalization and lysosomal degradation**, reduced AMPAR-mediated currents, impaired LTP, memory deficits (pqac-00000032, pqac-00000033, pqac-00000035) | Human clinical association + in vitro/in vivo mechanistic models | Graus 2016, doi: https://doi.org/10.1016/S1474-4422(15)00401-9; Ryding 2023, doi: https://doi.org/10.3390/cells13010015 (pqac-00000007, pqac-00000033) |
| **NMDAR (NR1)** | Cell-surface/synaptic glutamate receptor | Broader autoimmune encephalitis phenotype; may involve limbic symptoms including memory deficits, seizures, psychiatric symptoms; anti-NMDAR is a major AE subtype and included in limbic differential/criteria (pqac-00000001, pqac-00000004) | Ovarian teratoma association; positivity varies with age/sex in Graus table; review notes ovarian teratoma in **nearly 50%** of cases in some series, with lower tumor rates (~10%) in some countries (pqac-00000007, pqac-00000029) | IgG1-mediated **cross-linking, internalization, and lysosomal degradation** of NMDAR; suppression of NMDAR-dependent plasticity/LTP; altered excitability and receptor trafficking (pqac-00000032, pqac-00000037) | Human clinical cohorts + strong in vitro/in vivo mechanistic evidence | Graus 2016, doi: https://doi.org/10.1016/S1474-4422(15)00401-9; Ferreira 2024, doi: https://doi.org/10.1055/s-0044-1793933; Ryding 2023, doi: https://doi.org/10.3390/cells13010015 (pqac-00000007, pqac-00000029, pqac-00000037) |
| **Ma2** | Intracellular/onconeural antigen | **Paraneoplastic limbic encephalitis**; intracellular-antibody subgroup generally less responsive to immunotherapy than cell-surface forms (pqac-00000006, pqac-00000007) | **Testicular seminoma**; Graus table reports positivity **>95%** by Western blot (pqac-00000007) | Primarily a **marker of T-cell–mediated paraneoplastic autoimmunity** rather than a directly pathogenic surface-antibody mechanism (pqac-00000039, pqac-00000006) | Human clinical/paraneoplastic evidence | Graus 2016, doi: https://doi.org/10.1016/S1474-4422(15)00401-9; Ryding 2023, doi: https://doi.org/10.3390/cells13010015 (pqac-00000006, pqac-00000007, pqac-00000039) |
| **Hu (ANNA-1)** | Intracellular/onconeural antigen | Classic **paraneoplastic limbic encephalitis**/encephalomyelitis spectrum; intracellular high-risk antibody category with poorer response to immunotherapy (pqac-00000006, pqac-00000008) | Strongly cancer-associated; Graus identifies Hu as an onconeuronal antibody linked to cancer, though the supplied excerpt does not give a percentage for Hu specifically (pqac-00000006) | Mainly reflects **cytotoxic T-cell–mediated neuronal injury** rather than receptor internalization/signaling blockade (pqac-00000039, pqac-00000006) | Human clinical/paraneoplastic evidence | Graus 2016, doi: https://doi.org/10.1016/S1474-4422(15)00401-9; Canadian guideline 2024, doi: https://doi.org/10.1017/cjn.2024.16; Ryding 2023, doi: https://doi.org/10.3390/cells13010015 (pqac-00000006, pqac-00000008, pqac-00000039) |
| **GAD65** | Intracellular enzyme antigen | Limbic encephalitis/autoimmune epilepsy subgroup with predominant seizures; often younger median age in Graus discussion; usually no cancer, but cancer risk higher in older patients or with coexisting GABA<sub>B</sub>R antibodies (pqac-00000006) | Graus table reports approximate positivity **~25%** and associations with **thymoma** and **small-cell lung carcinoma** (pqac-00000007) | Intracellular target; direct pathogenicity less established than for surface antibodies, often treated as part of broader autoimmune process rather than classic receptor-internalization mechanism (pqac-00000036, pqac-00000039) | Human clinical evidence; mechanistic evidence less definitive | Graus 2016, doi: https://doi.org/10.1016/S1474-4422(15)00401-9; Ryding 2023, doi: https://doi.org/10.3390/cells13010015 (pqac-00000006, pqac-00000007, pqac-00000036) |


*Table: This table summarizes major antibody-defined subtypes relevant to autoimmune limbic encephalitis, including antigen class, typical clinical patterns, tumor associations, and supported mechanisms. It is useful for comparing cell-surface/synaptic versus intracellular paraneoplastic forms and linking subtype to diagnosis and management.*