Ta antibodies can occur in patients who present with limbic or brainstem encephalitis, sometimes associated with cerebellar dysfunction. In men, the presence of these antibodies suggests the presence of a germ-cell tumor, usually located in the testis. These autoimmune responses can be of particular interest to neurologists because the neurologic symptoms usually precede the tumor diagnosis.1
Clinically, the majority of patients with anti-Ta antibodies present with limbic dysfunction including short-term memory deficits, personality changes, irritability, depression, agitation, anxiety, and sleep disturbances. Partial complex or generalized seizures occur frequently. Hypothalamic dysfunction is common and may include hyperthermia, loss of libido and hypothyroidism. MRI or CT scans of the brain often demonstrate T2-weighted abnormalities in the medial aspects of the temporal lobes, but may be normal.1,2 Some patients may be misdiagnosed with viral encephalitis or a rapidly developing dementia.3 The course is usually progressive but can be relapsing and remitting.1,2
The presence of any of these findings raises the possibility of a paraneoplastic syndrome. The detection of anti-Ta antibodies in males strongly suggests the presence of testicular cancer. Anti-Ta antibodies have also been detected in women with cancer. However, to date, there is no correlation with a specific type of cancer and anti-Ta antibody detection in women.4 Therefore, the detection of anti-Ta antibodies in a woman should prompt the physician to consider a general search for a systemic cancer and close observation for those women in whom a neoplasm is not found.
- Identification of anti-Ta antibodies can confirm an autoimmune etiology for the neurologic symptoms. Reports suggest that either treatment of the associated tumor or immune modulation may ameliorate or stabilize the neurological symptoms.2
- A positive Ta Antibody Test in an adult patient suggests the presence of an underlying malignancy. In men, the primary consideration should be a testicular tumor. In women, a general evaluation for a systemic cancer should be considered.4
- Identification of presenting neurological symptoms as part of a paraneoplastic syndrome can lead to the early diagnosis of a potentially treatable cancer. Usually, in paraneoplastic syndromes symptoms of the neurologic disorder precede the diagnosis of the tumor.2
A 28-year-old man in previously good health developed a change in his personality, becoming anxious and irritable. Over a two-month period these symptoms worsened and he had several partial complex seizures. Within three months of symptom onset he had developed double vision and dysarthria. On examination he had severe difficulties with short-term memory and mild gait ataxia, as well as vertical gaze paresis, skew deviation and downbeating nystagmus. An EEG showed sharp waves in both temporal lobes. A CT scan of the head with and without contrast was normal but MRI demonstrated T2-weighted abnormalities in the mesial aspect of the left temporal lobe. The cerebrospinal fluid contained 43 cells (99% lymphocytes), a protein of 72 mg/dl, and 2 oligoclonal bands. Both serum and spinal fluid tested positive for the anti-Ta antibody. The patient was closely followed with serial testicular ultrasounds, which, while initially negative, demonstrated an area of abnormality in the right testis. The patient underwent orchiectomy and a small non-seminomatous germ-cell tumor was demonstrated. After surgery, the neurological symptoms partially improved.
Athena Diagnostics's Ta Autoantibody Test is based on the detection of polyclonal IgG antibodies that recognize the specific Ta antigen expressed in neurons and associated cancers. Athena's testing service employs a recombinant Ta antigen in a Western blot format that maximizes the specificity of test results. The use of a cloned recombinant antigen minimizes the chances of obtaining false positive results. Using Western blot to perform the test further reduces the likelihood of false positive results. Western blot analysis is a biochemical method that separates proteins by size. In the Western blot analysis, the Ta antigen will migrate to a specific molecular weight (40kDa). Evidence of a specific reaction between Ta antibodies in a patient's serum or CSF with the Ta recombinant protein antigen on the Western blot allows for the specific identification of Ta antibodies. Absence of a reaction indicates that Ta antibodies are not present in the test sample.6,7
There are several paraneoplastic antibodies that bind to the nucleus of neuronal cells. The more traditional immunohistochemical staining method of detecting paraneoplastic antibodies has relied on immunoreactivity of test serum with neurons in human or rat brain sections. The appearance of anti-Ta antibodies by this method is indistinguishable from that of anti-Ma. Therefore, immunohistochemistry cannot specifically identify anti-Ta antibodies. In addition, a similar immunohistochemical appearance can be seen with other antibodies of unknown significance.6,7
Reactivity of anti-Ta antibody at a 1:1000 dilution of sera is defined as a positive result. The Ta antibody may be found in patients with brainstem and/or limbic encephalitis, is sometimes associated with cerebellar dysfunction, and is associated with the presence of a variety of cancers. The Ta antibody is a highly-specific marker for paraneoplastic neurologic dysfunction. The detection of anti-Ta antibodies in a man is highly suggestive that the patient has or will develop a germ-cell tumor, usually of the testis.1 The detection of anti-Ta antibodies in a woman may suggest that she has or will develop a systemic cancer.4 The anti-Ta antibody has not been found in the sera of control subjects, including cancer patients without paraneoplastic neurologic disorders, patients with other neurological and autoimmune disorders (e.g., systemic lupus, multiple sclerosis), and healthy individuals.1,2
