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Paraneoplastic Autoantibodies

Paraneoplastic syndromes are autoantibody-mediated neurologic disorders associated with underlying tumors. These syndromes arise when systemic tumors express antigens normally found only in neural tissues. The immune system recognizes the tumor antigen as non-self, leading to the production of antibodies that recognize not only the tumor cells, but also any neural cells expressing the antigen. Neurologic symptoms often precede detection of the tumor. Detection of paraneoplastic syndrome antibodies should trigger a search for an underlying tumor, which often is occult by standard imaging techniques. Cancers most commonly associated with paraneoplastic syndromes include:

  • Small cell lung carcinoma
  • Ovarian carcinoma
  • Breast carcinoma
  • Thymoma
  • Hodgkin’s lymphoma

These autoantibodies are rarely detected in serum or CSF of healthy individuals or patients who have cancer without neurologic dysfunction.

Antineuronal Nuclear Antibody Type 1 (ANNA-1 or Anti-Hu)

Paraneoplastic encephalomyelitis is almost always associated with small cell lung carcinoma (SCLC). The relevant antibody (previously called anti- Hu) is termed anti-neuronal nuclear antibody type 1 (ANNA-1), and recognizes a 35-40 kD component found in neuronal cell nuclei.

ANNA-1 antibody is found almost exclusively in patients with a history of tobacco use or passive exposure. Women are affected twice as often as men. Cancer has been found in >90% of seropositive patients. Small cell lung carcinoma (SCLC) has been found in 83% of patients. A second malignant neoplasm is viagria from canada found in 13% of patients positive for ANNA-1 who have SCLC.

The most common clinical presentation of patients positive for ANNA-1 is peripheral neuropathy (sensory >sensorimotor>autonomic>>motor), but they can exhibit any element of televideocom.com encephalomyeloradiculopathy.  Approximately 10% of patients present with gastroparesis or intestinal obstruction. ANNA-1 has also been detected in children with intestinal dysmotility, cerebellar ataxia, and brainstem encephalitis with and lowest price on non generic levitra without neuroblastoma.

It is detected in 5 to 10% of patients with small cell lung carcinoma who do not have a paraneoplastic syndrome. ANNA-1 is not recommended as a screening test for lung cancer.

Serum is the preferred specimen. Specimen requirement is one red top or SST tube of blood. CSF results are sometimes positive when serum results are negative. If a lumbar puncture is going to be performed as part of the diagnostic workup, CSF testing is recommended to improve the pills store buy levitra detection rate.

Antineuronal Nuclear Antibody Type 2 (ANNA-2 or Anti-Ri)

Patients usually present with signs of midbrain, brain stem, cerebellar and/or spinal cord dysfunction. Ocular opsoclonus-myoclonus may be a prominent symptom. Paraneoplastic opsoclonus, characterized by involuntary rapid movement of the eyes in both vertical and horizontal planes, is most often associated with breast cancer and SCLC. The relevant antibody is termed anti-neuronal nuclear antibody type 2(ANNA-2), and recognizes a set of protein antigens of 55 and 80 kD found in neuronal cell nuclei. This autoantibody has also been detected in patients with bladder and cervical cancer.

Specimen requirement is one red top or SST tube of blood or CSF.

Antineuronal Nuclear Antibody Type 3 (ANNA-3)

This autoantibody causes paraneoplastic syndromes associated with SCLC. Fifteen percent of viagra canada cheap patients with SCLC will have a second malignancy. Reference Range is negative.

Purkinje Cell Cytoplasmic Antibody Type 1 (anti-PCA 1 or anti-Yo)

Paraneoplastic cerebellar degeneration is associated with breast or gynecological (ovarian, fallopian, endometrial) tumors. Less commonly it is trade name tramadol associated with lung (SCLC) cancer or Hodgkin lymphoma. More than 90% of seropositive patients present with subacute cerebellar ataxia and approximately 5% present with sensorimotor or motor neuropathy.

PCA-1 antibody is rarely found in patients with neurologic diseases without breast or gynecologic cancer. Conversely it is rarely found in patients with breast or gynecologic cancer without neurologic dysfunction. Reference range is negative.

Purkinje Cell Cytoplasmic Antibody Type 2 (anti-PCA 2)

This autoantibody is usually associated with lung cancer, especially SCLC. If lung cancer is not detected, an extrapulmonary primary SCLC should be considered. The antibody is seldom detected in patients with uncomplicated SCLC. Reference range is negative.

Purkinje Cell Cytoplasmic Antibody Tr (anti-PCA-Tr)

This autoantibody has only been detected in 80% of patients with Hodgkin lymphoma and causes subacute cerebellar ataxia. Anti-Tr antibody titer tends to drop after treatment of Hodgkin's disease.

Amphiphysin antibody IgG

Amphiphysin antibody is present in about 5 percent of patients with stiff person syndrome and may cause paraneoplastic neurological syndrome associated with small-cell lung cancer and breast tumors.

CRMP-5 IgG

CRMP is also called CV2. CRMP is an oligodendrocyte cytoplasmic antigen. IgG autoantibody to this antigen causes a paraneoplastic syndrome in patients with SCLC, thymoma or renal cell carcinoma. Clinical manifestations include cerebellar degeneration, uveitis, and peripheral neuropathy, which is usually sensorimotor.

Antibody titer usually decreases after treatment of the neoplasm. A rising titer is indicative of tumor persistence or recurrence.

Ta

Antbodies to Ta are present in patients with testicular cancer who present with limbic and link for you brain stem encephalitis. These antibodies have also been reported in patients with breast and lung cancers.

Recoverin

Recoverin is a calcium binding protein that is cheap viagra canada expressed in photoreceptors in the retina. Antibodies to viagra for sale online recoverin cause cancer associated retinopathy (CAR), which is most commonly associated with SCLC. CAR is characterized by sudden unexplained loss of vision associated with a high titer of antibody against recoverin.

P/Q Voltage-Gated Calcium Channel

Voltage-gated calcium channel (VGCC) is a large transmembrane protein with multiple subunits that are named P, Q, N, L, T and R. P/Q channels play a role in release of acetylcholine from nerve endings, while N type channels are key components of the autonomic conduction system. P/Q-type VGCCs make up greater than 95 percent of the functioning receptors at the neuromuscular junction.

Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon disorder of cialis testimonial neuromuscular junction transmission that causes slowly progressive symmetrical proximal muscle weakness.  Autonomic dysfunction such as dry eyes, dry mouth, impaired sweating and erectile dysfunction may also be present. Early recognition is particularly important because approximately 50% of cases are associated with a malignancy, mainly small cell lung cancer (SCLC).

Diagnosis of LEMS is confirmed by electrophysiology studies and testing for the presence of antibodies to voltage-gated calcium channel (VGCC). Antibodies against P/Q-type VGCC are present in approximately 85 to 95 percent of patients and antibodies against N-type VGCC are found in about 30 to 40 percent of patients with LEMS. Antibodies directed against VGCC interfere with the normal calcium flux required for the release of acetylcholine. Synaptic transmission fails when antibodies cause a critical loss of calcium channels.

A high titer P/Q-type VGCC antibody is strongly suggestive of LEMS in patients with a high pretest probability of LEMS. It is important to realize that P/Q-type VGCC antibodies are present in a variety of other diseases. Low tittered antibodies are present in some patients with myasthenia gravis, amyotrophic lateral sclerosis and other autoimmune diseases. They also may be detected in paraneoplastic disorders associated with lung, ovarian, or breast carcinoma. Thus, while the VGCC antibody test is confirmatory in patients with clinical and electrophysiologic features of LEMS, the antibody test alone is not diagnostic, especially in the presence of malignancy or amyotrophic lateral sclerosis.

Antibodies may not be present at onset of cialis from india LEMS. Testing should be repeated later if clinical suspicion remains high. Titers are generally higher in patients with severe weakness, but severity cannot be predicted by antibody titer.

Calcium channel binding antibodies (IgG and IgM) are measured quantitatively by immunoprecipitation assays. Serum is the preferred specimen. However, antibody may be detected in cerebrospinal fluid when serum results are negative. If a spinal tap has been already been performed, it is recommended that CSF be submitted with serum and http://bloesemkinderopvang.nl/viagra-cost tested if serum is negative.

VGKC complex IgG

Antibodies to voltage-gated potassium channel (VGKC) were originally associated with autoimmune limbic encephalitis. More recently, they have been found to cause rapid cognitive decline resembling frontotemporal dementia and Creutzfeldt-Jakob disease. These antibodies are also cause paraneoplastic neurological syndromes associated with small cell lung carcinoma, thymoma, breast adenocarcinoma and prostate cancer. VGKC IgG is more commonly detected in serum than in CSF.

VGKC antibodies can be distinguished from antibodies to leucine-rich, glioma-inactivated 1 protein (Lgi1) and contactin-associated protein-2 (Caspr-2) by Western blot.

GAD65

Glutamic acid decarboxylase (GAD) is an enzyme involved in the synthesis of the neurotransmitter, gamma-aminobutyric acid (GABA). GAD65 antibody is the most frequently detected pancreatic islet antibody occurring in 70 to 80% of new onset type 1 diabetes cases. Detection of GAD65 antibody in non-diabetic individuals predicts later development of type 1 diabetes. It is also helpful in distinguishing between patients with type 1 and type 2 diabetes in adults. GAD65 autoantibody also serves as a marker of predisposition to other autoimmune disease that occur with type 1 diabetes such as Graves' disease, Hashimoto's thyroiditis, hypothyroidism, pernicious anemia, premature ovarian failure, Addison's disease and vitiligo.

GAD65 antibodies are not specific for type 1 diabetes and may be present in patients with a variety of autoimmune neurologic disorders including stiff-man syndrome, neuromyelitis optica, myasthenia gravis, Lambert-Eaton syndrome and dysautonomia. Tumors associated with GAD65 antibodies include thymoma, renal cell carcinoma, breast cancer and colon adenocarcinoma. Approximately 3% of the general population has detectable GAD65 antibodies.

AGNA

Anti-glial/neuronal antibody, also known as Sox-1 antibody is associated with small cell lung carcinoma.

NMDA receptor

NMDA receptor antibody is detected in approximately 50% of women with ovarian teratoma. Only 2% have a neoplasm other than ovarian teratoma. These other neoplasms include breast adenocarcinoma, ovarian neuroendocrine tumors, sex cord stromal tumor, pseudopapillary neoplasm of pancreas, neuroblastoma, and Hodgkin lymphoma. Neoplasia has been documented in 5% of men with NMDA receptor antibody; either testicular germ cell tumors or small-cell lung carcinoma. The female:male ratio of patients is about 8:1. This antibody is more commonly detected in CSF than in serum.

Patients with NMDA-receptor antibody often present with headache, fever, nausea, vomiting, diarrhea, or upper respiratory tract symptoms. Shortly afterwards, they develop psychiatric symptoms including anxiety, insomnia, fear, delusions, mania, and paranoia. Movement disorders include oro-lingual-facial dyskinesias, generalized chorea, oculogyric crisis, dystonia, and rigidity. Autonomic manifestations include hyperthermia, tachycardia, hypersalivation, hypertension, bradycardia, hypotension, urinary incontinence, and erectile dysfunction.

AMPA receptor Antibody

Alpha-Amino-3-Hydroxyl-5-Methyl-4-Isoxazolepropionic acid (AMPA) receptors are glutamate receptors that mediate fast excitatory neurotransmission in the brain. Antibodies targeting the extracellular domains of either or both GluR 1 or GluR2 (GluA1 or GluA2) subunits have been associated with limbic encephalitis. Patients usually present with seizures, memory loss, mood changes, personality changes, psychosis, delirium or sleep disorders. A history of autoimmune disorders, cancer, or cancer risk factors increase the generic for cialis likelihood of good choice autoimmune etiology.

Antibody can be detected in both serum and CSF. If antibody is detected in serum, subsequent testing of CSF adds little value. However, patients with negative serum results sometimes have positive CSF results. High titer antibodies are more specific for limbic encephalitis.

AMPA receptor antibody is detected using immunofluoresence to detect IgG binding to human cells transfected with GluR 1 and GluR2 receptor subunits. Transfected cells over-express the cognate protein, increasing the sensitivity of the test. Specimen requirements are a red top tube of blood for serum antibody and 1 mL of CSF in a sterile vial for CSF antibody..

Patients with limbic enephalitis due to cheap levitra order prescription AMPA receptor antibody may also have other coexisting autoantibodies such as anti-CRMP5, anti-GAD65 and anti-AGNA/SOX1.

GABA B receptor

Antibody targeting the B1 subunit of the gamma-aminobutyric acid-type B (GABA-B) receptor has been reported in patients with limbic encephalitis characterized by psychiatric symptoms and prominent seizures. Approximately 50% of antibody positive patients have small cell lung carcinoma (SLCL). Men and buy generic brand advair diskus women are affected equally. The mean age of onset is 60 years.

Patients usually present with seizures, memory loss, mood changes, personality changes, psychosis, delirium or sleep disorders. The likelihood of an autoimmune etiology is increased if a patient has a history of autoimmune disorders, cancer, or cancer risk factors such as smoking.

Patients with GABA-B-R receptor antibodies may have other coexisting antibodies such as N type calcium channel antibody, GAD65 antibody, thyroid antibodies, and GNA/SOX 1 antibody

Antibody can be detected in both serum and CSF. If antibody is detected in serum, subsequent testing of CSF adds little value. However, patients with negative serum results sometimes have positive CSF results. High titer antibodies are more specific for limbic encephalitis.

GABA-B receptor antibody is detected using immunofluoresence to detect IgG binding to human cells transfected with B1 subunit of the GABA type B receptor. Transfected cells over-express the cognate protein, increasing sensitivity of the test. Specimen requirements are a red top tube of blood for serum antibody and 1 mL of CSF in a sterile vial for CSF antibody.

NMO IgG

Neuromyelitis optica (NMO), also known as Devic's disease and optic-spinal multiple sclerosis, is a severe idiopathic inflammatory demyelinating disease that selectively affects optic nerves and the spinal cord. It typically spares the brain, and generally follows a relapsing course. Within 5 years, 50% of patients lose functional vision in at least 1 eye or are unable to walk independently. In North America, the proportion of nonwhite individuals is higher among patients with NMO than among those with classic multiple sclerosis.

Many patients with NMO are misdiagnosed as having multiple sclerosis. Accurate diagnosis is important because prognosis and treatment for the two diseases differ. NMO typically has a worse outcome than multiple sclerosis due to early and frequent relapses. NMO is treated with immunosuppression while multiple sclerosis is treated with immunodulation. Plasmapheresis is more beneficial for patients with NMO than for those with multiple sclerosis.

Early diagnosis and treatment are important to reduce the morbidity of NMO. Patients with NMO produce an antibody to aquaporin-4, a water channel protein located in astrocytes. Seropositivity for NMO autoantibody IgG (NMO-IgG) allows early

diagnosis of http://www.mon-cours-de-piano.com/best-prices-on-brand-viagra NMO (73% positive; 91% specific). NMO-IgG is uniformly negative inpatients with classical multiple sclerosis. A positive value is consistent with NMO or a related disorder and justifies initiation of early immunosuppressive therapy.

Approximately 40% of adult patients with longitudinally-extensive transverse myelitis are seropositive for NMO-IgG, while approximately 15-20% of patients with multiple episodes of optic neuritis test positive. Seropositive patients are much more likely to relapse or progress within 2 years than seronegative patients. Seronegativity does not exclude the diagnosis of NMO. Patients already treated with immmunosuppressive therapy may not have detectable antibody.

Specimen Recommendation

Some antibodies are more frequently detected in plasma, while others are more likely to be detected in CSF. Therefore, some laboratories recommend testing for these antibodies in both serum and CSF to maximize diagnostic yield.

Reference value is no antibody detected for each of these antibodies.

 

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