Basic Neuroscience · Neuropathology
Autoantibodies in Neurology
Diagnostic autoantibodies in neurological disease, grouped by category. Each lists the associated disorder(s) and the target antigen with key clinical pearls.
| Antibody | Disease | Target / Description |
|---|---|---|
| Demyelinating CNS | ||
| AQP4 Ab | Neuromyelitis optica (NMO) | Aquaporin-4. |
| MOG Ab | Childhood MS, ADEM, AQP4-negative NMO, AQP4-negative optic neuritis | Myelin oligodendrocyte glycoprotein. |
| Neuromuscular junction & muscle | ||
| AChR Ab | Myasthenia gravis | Acetylcholine-receptor antibody. Positive in 85% of myasthenia patients. |
| MuSK Ab | Myasthenia gravis | Muscle-specific kinase antibody → inhibits AChR clustering at the motor end plate. Positive in ~50% of AChR-negative patients. More common in women and African Americans; no eye involvement, more neck and bulbar involvement; less responsive to anticholinesterase medications or thymectomy. |
| LRP4 Ab | Myasthenia gravis | LDL receptor-related protein 4 — a receptor for neural agrin that activates MuSK. Positive in ~9% of double-seronegative patients (AChR- and MuSK-negative). |
| Striational Ab (RyR / Titin Ab) | Myasthenia gravis | Against striated-muscle proteins (titin and ryanodine receptor). Present only in AChR-positive myasthenia, usually elderly (>60) and patients with thymoma. Sensitive but not specific for thymoma (50% of positives have thymoma; 95% of thymoma patients have titin Ab). Associated with a more severe course; respond to calcineurin inhibitors (tacrolimus, cyclosporine). Anti-RyR can react against both skeletal RyR1 and cardiac RyR2 receptors. |
| VGCC Ab | Lambert-Eaton myasthenic syndrome (LEMS) | Positive in 90% of LEMS. Associated with SCLC — screen with CXR every 6 months for lung cancer. |
| GAD | Stiff-person syndrome; SPS-plus (PERM) | Glutamic acid decarboxylase. |
| Glycine receptor Ab | Stiff-person syndrome-plus / "PERM" (progressive encephalomyelitis with rigidity and myoclonus) | Against the glycine receptor. |
| Channels / surface antigens | ||
| VGKC (CASPR2) | Isaacs syndrome (neuromyotonia); Morvan syndrome (neuromyotonia, encephalopathy, hyperhidrosis); limbic encephalitis | Contactin-associated protein-2. |
| VGKC (LGI-1) | Limbic encephalitis | Leucine-rich, glioma-inactivated protein 1. Brief faciobrachial dystonic seizures, memory loss, disorientation, hyponatremia in 60%. CSF lymphocytosis and oligoclonal bands in 50%. |
| NMDA | NMDA-receptor encephalitis | Psychiatric features, cognitive dysfunction, seizures. May be associated with ovarian teratoma — obtain pelvic MRI. |
| DPPX | DPPX-associated encephalitis | Dipeptidyl-peptidase-like protein 6, a peptide related to VGKC responsible for attenuation of back-propagation of action potentials. Starts with diarrhea and weight loss, followed by CNS hyperexcitability (hyperekplexia, myoclonus, seizures) over a few months. |
| Onconeuronal (paraneoplastic) antibodies | ||
| Amphiphysin | Stiff-person syndrome (paraneoplastic) | SCLC & breast cancer. Protein present on the cytoplasmic surface of synaptic vesicles. |
| Hu (ANNA-1) | Encephalomyelitis (limbic, brainstem, cortical, myelitis); sensory peripheral neuronopathy; cerebellar degeneration | SCLC & neuroblastoma. Directed against a neuronal nuclear protein (present in all neurons). |
| Yo | Cerebellar degeneration | Ovarian, endometrial & breast cancer. |
| Ri (ANNA-2) | Cerebellar degeneration; opsoclonus | Ovarian, endometrial & breast cancer. Directed against the NOVA protein. Most common cause of opsoclonus in adults: anti-Hu, Ri, Yo (SCLC & breast). In children: neuroblastoma, usually with negative anti-Hu/Ri/Yo. |
| Ma2 | Cerebellar degeneration; limbic encephalitis; stiff-person syndrome | Testicular tumors. |
| CV2 (CRMP5) | Cerebellar degeneration; limbic encephalitis; peripheral neuropathy | SCLC, thymoma & uterine sarcoma. |
| Glycoproteins / gangliosides | ||
| GQ1b | Miller-Fisher syndrome; GBS with ophthalmoplegia; Bickerstaff encephalitis; pharyngo-cervical-brachial GBS | Positive in 90% of patients with Miller-Fisher syndrome. |
| GM1 | AMAN; AMSAN; multifocal motor neuropathy (MMN) | Associated with axonal variants of GBS. |
| GD1b | Pure sensory variant of GBS | Against gangliosides on sensory neurons in the dorsal root ganglia. |
| MAG | Anti-MAG neuropathy (chronic sensorimotor demyelinating neuropathy); multiple sclerosis; SLE; MGUS / Waldenström | Myelin-associated glycoprotein (present in peripheral and central myelin). Present in 50% of patients with monoclonal gammopathy (MGUS or Waldenström) and peripheral neuropathy → test for MAG in MGUS/Waldenström patients with neuropathy. |
| Other | ||
| Endothelial cell Ab | Susac syndrome | Triad of encephalopathy, branch retinal artery occlusion, and hearing loss. |
| SSA (Ro) / SSB (La) | Sjögren syndrome | Axonal neuropathy (pure sensory or sensorimotor), sensory ganglionopathy, small-fiber neuropathy, autonomic neuropathy. SSA/SSB are positive in only 40% of Sjögren patients presenting with neurological disease. |
LIGHTS on RITE by Ahmed Koriesh