Version October 2024
| Antibody (alternative name) | Likely pathogenic mechanism | Neurologic phenotypes | Frequency of cancer (%) | Usual tumors | Sex, age-related, and other specificities |
| High-risk antibodies (>70% associated with cancer) | |||||
| Hu (ANNA-1) | T cell-mediated | Sensory neuronopathy, chronic gastrointestinal pseudo-obstruction, encephalomyelitis, limbic encephalitis | 85 | SCLC >> NSCLC, other neuroendocrine tumors, neuroblastoma | Limbic encephalitis is usually nonparaneoplastic in patients <18 years of age. |
| CV2/CRMP5 | T cell-mediated | Encephalomyelitis, sensory neuronopathy | >80 | SCLC, thymoma | Patients with an associated thymoma are younger and present less commonly with neuropathy. |
| SOX1 | Uncertain | LEMS with and without rapidly progressive cerebellar syndrome | >90 | SCLC | Stronger correlation with SCLC than with a particular neurologic presentation. |
| PCA-2 (MAP1B) | T cell-mediated | Sensorimotor neuropathy, rapidly progressive cerebellar syndrome, encephalomyelitis | 80 | SCLC, NSCLC, breast cancer | |
| Amphiphysin | Uncertain; possibly antibody-mediated | Polyradiculopathy, sensory neuronopathy, encephalomyelitis, stiff-person syndrome | 80 | SCLC, breast cancer | Associated antibodies commonly coexist. Patients with isolated antiamphiphysin are more likely to be females with breast cancer and stiff-person syndrome. |
| Ri (ANNA-2) | T cell-mediated | Brainstem/cerebellar syndrome, opsoclonus-myoclonus-ataxia syndrome | >70 | Breast > lung (SCLC and NSCLC) | Breast cancer in females; lung cancer in males. |
| Yo (PCA-1) | T cell-mediated | Paraneoplastic cerebellar degeneration | >90 | Ovarian cancer, breast cancer | Almost all female; in males, antigen expression by tumor should be proven. |
| Ma2 and/or Ma | T cell-mediated | Limbic encephalitis, diencephalitis, brainstem encephalitis | >75 | Testicular cancer, NSCLC | Young males: testicular tumors and isolated Ma2 positivity; older patients: SCLC and both Ma1/2 positivity. |
| Tr (DNER) | Uncertain | Paraneoplastic cerebellar degeneration | 90 | Hodgkin lymphoma | |
| KLHL11 | T cell-mediated | Brainstem/cerebellar syndrome | 80 | Testicular cancer | Young males. |
| Intermediate-risk antibodies (30 to 70% associated with cancer) | |||||
| AMPAR | Antibody-mediated | Limbic encephalitis | >50 | SCLC, malignant thymoma | Paraneoplastic origin is more likely when other onconeuronal antibodies co-occur. |
| GABABR | Antibody-mediated | Limbic encephalitis | >50 | SCLC | Paraneoplastic cases are more commonly observed in older males, in smokers, and in association with anti-KCTD16 antibodies. Most cases in young patients are not paraneoplastic. |
| mGluR5 | Antibody-mediated | Encephalitis | ~50 | Hodgkin lymphoma | |
| P/Q VGCC | Antibody-mediated for LEMS; uncertain for cerebellar syndrome | LEMS, rapidly progressive cerebellar syndrome | 50 (LEMS; nearly 90 for rapidly progressive cerebellar syndrome) | SCLC | Co-occurrence with N-type VGCC antibodies might be slightly more common in paraneoplastic LEMS. |
| NMDAR | Antibody-mediated | Anti-NMDAR encephalitis | 38 | Ovarian or extraovarian teratomas | Tumor (mostly ovarian teratomas) predominates in females 18 to 45 years of age (50%). Older patients less frequently have tumors (<25%), usually carcinomas. Paraneoplastic cases in children are very rare (<10%). |
| Caspr2 | Antibody-mediated | Morvan syndrome, limbic encephalitis, acquired neuromyotonia (Isaac syndrome) | 50 (for Morvan syndrome) <30 (for all other syndromes) | Malignant thymoma | Caspr2 should be considered as an intermediate-risk antibody only in the setting of Morvan syndrome. When associated with other neurologic syndromes, the risk of cancer is very low. |
| Lower-risk antibodies (<30% associated with cancer) | |||||
| mGluR1 | Antibody-mediated | Isolated cerebellar ataxia | 11 | Mostly hematologic | |
| GABAAR | Antibody-mediated | Encephalitis | <30 | Malignant thymoma | Paraneoplastic origin is less frequent in children (10%) than in adults (60%). |
| GFAP | Uncertain | Meningoencephalitis | ~20 | Ovarian teratomas, adenocarcinomas | May occur as an immunologic accompaniment in anti-NMDAR encephalitis with ovarian teratomas. |
| GAD65 | Uncertain | Limbic encephalitis, stiff-person syndrome, cerebellar ataxia | <15 | SCLC, other neuroendocrine tumors, malignant thymoma | Paraneoplastic origin more likely in older patients, males, and in association with neuronal antibodies or atypical clinical presentations. |
| LGI1 | Antibody-mediated | Limbic encephalitis | <10 | Malignant thymoma, neuroendocrine tumors | Paraneoplastic cases are mainly observed in patients with Morvan syndrome and both serum LGI1 and Caspr2 antibodies. |
| DPPX | Antibody-mediated | Encephalitis with CNS hyperexcitability, PERM | <10 | B cell neoplasms | |
| GlyR | Antibody-mediated | Limbic encephalitis, PERM | <10 | Malignant thymoma, Hodgkin lymphoma | |
| AQP4 | Antibody-mediated | Neuromyelitis optica spectrum disorder | <5 | Adenocarcinomas | Paraneoplastic origin associated with older age, male sex, and severe nausea/vomiting at onset. |
| MOG | Uncertain | MOG antibody-associated disease | 5 cases reported | Mostly ovarian teratomas | |
| AK5 | T cell-mediated | Limbic encephalitis | 0 | No known cancer association | |
| GluK2 | Antibody-mediated | Encephalitis with prominent cerebellar involvement | <1 | 1 of 8 patients had a remote history of Hodgkin lymphoma | |
| SEZ6L2 | Uncertain | Subacute cerebellar syndrome with extrapyramidal symptoms | 0 | Only 6 cases reported | |
AK5: adenylate kinase 5; AMPAR: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; ANNA: antineuronal nuclear antibody; AQP4: aquaporin 4; Caspr2: contactin-associated protein-like 2; CNS: central nervous system; CRMP5: collapsin-responsive mediator protein 5; DNER: delta/notch-like epidermal growth factor-related receptor; DPPX: dipeptidyl-peptidase-like protein; GABAAR: gamma-aminobutyric acid-A receptor; GABABR: gamma-aminobutyric acid-B receptor; GFAP: glial fibrillary acidic protein; GAD: glutamic acid decarboxylase; GluK2: glutamate kainate receptor subunit 2; GlyR: glycine receptor; KCTD16: potassium channel tetramerization domain containing; KLHL11: Kelch-like protein 11; LGI1: leucine-rich glioma inactivated protein 1; LEMS: Lambert-Eaton myasthenic syndrome; MAP1B: microtubule-associated protein 1B; MG: myasthenia gravis; mGluR1: metabotropic glutamate receptor 1; mGluR5: metabotropic glutamate receptor 5; MOG: myelin oligodendrocyte glycoprotein; NMDAR: N-methyl-D-aspartate receptor; NSCLC: non-small cell lung cancer; PCA: Purkinje cell antibody; PERM: progressive encephalomyelitis with rigidity and myoclonus; P/Q VGCC: P/Q type voltage-gated calcium channel; SCLC: small cell lung cancer; SEZ6L2: seizure-related 6 homolog like 2; SOX1: SRY-box transcription factor 1.
* Antibodies to mGluR2 are not listed as there is an insufficient number of cases to determine risk of cancer association.Do you want to add Medilib to your home screen?
