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Antibody screening tests can be used to detect autoimmune diseases and types of cancer. The Mayo chart outlines the decision making rationale for the types of tests done. Antibody screening can be especially helpful in SPS plus paraneoplastic syndrome and SPS plus PERM.
Mayo Clinic Paraneoplastic Evaluation Algorithm
Antibodies to 128-kd synaptic protein localized in neurons and concentrated at synapses were found in three women with stiff-person syndrome and breast cancer. All were anti-GAD negative. None had concurrent autoimmune disease.
AGNA antibodies are associated with neuropathy, Lambert-Eaton myasthenic syndrome, and limbic encephalitis and are found in cases of small-cell neuroendocrine carcinoma.
ANNA 3 antibodies are associated with brainstem encephalitis, limbic encephalitis, myelopathy, and peripheral neuropathy, and are found in small-cell lung cancer.
Anti-AChR antibodies are associated with Lambert-Eaton myasthenic syndrome and are found in cases of thymoma.
Anti-amphiphysin antibodies are most often associated with stiff-person syndrome, sensory neuronopathy, encephalomyelitis, limbic encephalitis, aphasia, subacute onset dementia, myelopathy, neuropathy, and cerebellar ataxia and are found in breast adenocarcinoma and small-cell lung cancer.
Anti-CAR antibodies are associated with retinopathy and are found in cases of breast and small-cell lung cancers.
Anti-GABA-β antibodies are associated with limbic encephalitis and seizures and are found in small cell lung cancer and neuroendocrine tumors.
Anti-GABARAP (GABA-α receptor associated protein) associates with GABA-α Rg2 to link GABA-α receptors to the cytoskeleton. It is associated with stiff-person syndrome.
Anti-GAD65 GAD65 forms a complex with Heat Shock Cognate 70 (HSC70), cysteine string protein (CSP) and Vesicular GABA transporter VGAT, which, as a complex, helps package GABA into vesicles for release during neurotransmission. GAD65 antibodies are associated with stiff-person syndrome, diabetes, cerebellar ataxia, seizures, limbic encephalitis, brainstem encephalitis, opthalmoplegia, parkinsonism, myelopathy, and are found in thymoma, Hodgkin’s lymphoma, renal-cell, breast, small-cell lung, and colon cancers.
Anti-GAD67 GAD67 synthesizes GABA for neuron activity unrelated to neurotransmission, such as synaptogenesis and protection from neural injury and is found less often and in smaller quantities in stiff-person syndrome.
Anti-ganglioside (GM 1) Antibody (IGM) are are found in autoimmune neuropathies, dementia, celiac disease, multiple sclerosis, rheumatoid arthritis, primary Sjögren's syndrome, systemic lupus erythematosus, and certain forms of Guillain-Barré syndrome.
Anti-gephyrin antibodies are also sometimes found in SPS patients. The antibodies appear to interact with antigens in the brain neurons and the spinal cord synapses, causing a functional blockade with GABA.
Anti-glycine receptor antibodies are associated with stiff-person syndrome and are found in cases of thymoma and Hodgkin’s lymphoma.
Anti-Hu (ANNA 1) antibodies are most often associated with sensory neuropathy, encephalomyelitis, chronic gastric pseudoobstruction, cerebellar ataxia, limbic encephalitis, and small-cell lung cancer.
Anti-Ma1 and 2 antibodies are associated with limbic encephalitis, hypothalamic disorder, and brainstem encephalitis, and found in cases of testicular, breast, and colon cancer.
Anti-MGlur1 antibodies are associated with cerebellar ataxia and found in cases of Hodgkin’s lymphoma.
Anti-MGlur5 antibodies are associated with limbic encephalitis and found in cases of Hodgkin’s lymphoma.
Anti-MuSK antibodies are associated with myasthenia gravis. Autoantibodies form against the MuSK protein (muscle specific kinase), a tyrosine kinase receptor which is required for the formation of the neuromuscular junction. Antibodies against MuSK inhibit the signaling of MuSK normally induced by its nerve-derived ligand, agrin. The result is a decrease in patency of the neuromuscular junction, and the consequent symptoms of myasthenia gravis.
Anti-PCA1 antibodies are associated with cerebellar ataxia, brainstem encephalitis, Lambert-Eaton syndrome, peripheral and autonomic neuropathies and found in Mullerian adenocarcinoma and breast adenocarcinoma.
Anti-PCA2 antibodies are associated with limbic encephalitis, ataxia, brainstem encephalitis, Lambert-Eaton syndrome, peripheral and autonomic neuropathies and found in cases of small-cell lung cancer.
Anti-Ri (ANNA 2) antibodies are most often associated with ospomyoclonus, cerebellar ataxia, brainstem encephalitis, dementia, limbic encephalitis, myelopathy, and peripheral neuropathy, and found in breast and small-cell lung cancers.
Anti-Tr antibodies are associated with cerebellar ataxia and found in cases of Hodgkin’s lymphoma.
Anti-VGKC antibodies are associated with Lambert Eaton myasthenic syndrome and neuromyotonia and found in cases of thymoma and small-cell lung cancer.
Anti-VGCC antibodies are associated with Lambert Eaton myasthenic syndrome and paraneoplastic cerebellar degeneration and found in cases of small-cell lung cancer.
Anti-Yo (PCA 1) antibodies are most often associated with subacute cerebellar ataxia, sensory-motor neuropathy, uveitis, retinopathy, and encephalomyelitis. They are found in thymomas, and ovarian, breast, uterine, and small-cell lung cancers.
Anti-Zic4 antibodies are associated with paraneoplastic cerebellar degeneration and found in Hodgkin’s lymphoma.
CRMP-5 antibodies are associated with subacute onset dementia, personality change, aphasia, depression, chorea, ataxia, myelopathy, radiculopathy, neuropathy, Lambert-Eaton myasthenic syndrome and found in cases of small-cell lung cancer and thymoma.
Myelin Associated Glycoprotein (MAG) AB with REFL antibodies attack and disrupt the function of myelin associated glycoproteins. They are associated with a specific type of peripheral neuropathy. As Schwann cells are destroyed by antibodies, the nerve cells in the surrounding region begin to lose function and exhibit muscle weakness, sensory problems, and other motor deficits usually starting as hand tremor s or trouble walking. The disorder occurs in only 10% of those afflicted with peripheral neuropathy. The antibodies are also associated with amyloidosis, thymoma, myasthenia gravis. ELISA is considered the most accurate method of measurement.
Purkinje Cell Cytoplasmic Ab, Type 1, 2, and Tr (aka Anti-Yo, Anti-Hu, Anti-Tr) are associated with paraneoplastic cerebellar degeneration (PCD) seen in lung, ovarian, breast, Hodgkin’s lymphoma and other cancers. PCD occurs in less than 1% of cancer patients and usually occurs in middle-aged women. It is thought to be triggered when tumor cells express a protein normally expressed in the Purkinje neuronal protein termed CDR2.
PCD patients harbor an anti-neuronal antibody known as anti-Yo. PCD may be associated with onconeural antibodies directed against other intracellular antigens or against cell surface and with other tumors. When associated with small cell lung cancer, it is termed "anti-Hu" (more commonly associated with paraneoplastic subacute sensory neuropathy and/or limbic encephalitis).
The immune cells cross the blood–brain barrier, resulting in an autoimmune attack of Purkinje cells throughout the cerebellar cortex. Other paraneoplastic antibodies may be associated with PCD symptoms, including anti-Tr and antibodies to glutamate receptors.
Occasionally myoclonus and opsoclonus may occur. Neurological symptoms manifested by dysarthria, truncal, limb and gait ataxia, vertigo, nausea, vomiting, diplopia, and nystagmus present insidiously and progress rapidly for about 6 months to a severely disabled state followed by a variable plateau period that can last for months to years.
For more information on these tests, visit Quest Labs.
ANTIBODY SCREENING