A Serologic Marker of Paraneoplastic Limbic and Brain-Stem Encephalitis in Patients with Testicular Cancer

TLDR

Limbic and brain‑stem dysfunction in cancer patients can arise from paraneoplastic syndromes, occurring more frequently with testicular cancer than most other cancers. The study aimed to identify antineuronal antibodies that could serve as a diagnostic marker for paraneoplastic limbic and brain‑stem encephalitis in testicular cancer patients. Using immunohistochemistry, immunoblotting, cDNA library screening, and Northern blotting, the authors cloned a 40‑kDa neuronal antigen (Ma2) and demonstrated that 10 of 13 patients had antibodies against it, whereas 344 controls did not. Antibodies to Ma2, a protein selectively expressed in normal brain and testicular tumors and homologous to Ma1, were present in patient serum and cerebrospinal fluid, supporting a paraneoplastic etiology and offering potential diagnostic value.

Abstract

In patients with cancer, symptoms of limbic and brain-stem dysfunction may result from a paraneoplastic disorder. Paraneoplastic limbic or brain-stem encephalitis occurs more frequently with testicular cancer than with most other cancers. We sought antineuronal antibodies that might be used in a diagnostic test for this syndrome.Immunohistochemical and immunoblotting techniques were used to detect serum and cerebrospinal fluid antibodies. Serologic screening of a complementary DNA library and Northern blotting were used to clone the target antigen and determine which tissues expressed it.Of 13 patients with testicular cancer and paraneoplastic limbic or brain-stem encephalitis (or both), 10 had antibodies in serum and cerebrospinal fluid against a 40-kd neuronal protein. These antibodies were used to clone a gene that we call Ma2, which codes for a protein (Ma2) that was recognized by serum from the 10 patients, but not by serum from 344 control subjects. Ma2 was selectively expressed by normal brain tissue and by the testicular tumors of the patients. Ma2 shares homology with Ma1, a "brain-testis-cancer" gene related to other paraneoplastic syndromes and tumors.The serum of patients with subacute limbic and brain-stem dysfunction and testicular cancer contains antibodies against a protein found in normal brain and in testicular tumors. Detection of these antibodies supports the paraneoplastic origin of the neurologic disorder and could be of diagnostic importance.