A serologic marker of paraneoplastic limbic and brain-stem encephalitis inpatients with testicular cancer

Background In patients with cancer, symptoms of limbic and brain-stem dysfu nction 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 us ed in a diagnostic test for this syndrome. Methods Immunohistochemical and immunoblotting techniques were used to dete ct serum and cerebrospinal fluid antibodies. Serologic screening of a compl ementary DNA library and Northern blotting were used to clone the target an tigen and determine which tissues expressed it. RESULTS Of 13 patients with testicular cancer and paraneoplastic limbic or brain-stem encephalitis (or both), 10 had antibodies in serum and cerebrosp inal 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 rec ognized by serum from the 10 patients, but not by serum from 344 control su bjects. Ma2 was selectively expressed by normal brain tissue and by the tes ticular tumors of the patients. Ma2 shares homology with Ma?, a "brain-test is-cancer" gene related to other paraneoplastic syndromes and tumors. Conclusions The serum of patients with subacute limbic and brain-stem dysfu nction and testicular cancer contains antibodies against a protein found in normal brain and in testicular tumors. Detection of these antibodies suppo rts the paraneoplastic origin of the neurologic disorder and could be of di agnostic importance. (N Engl J Med 1999;340:1788-95.) (C) 1999, Massachuset ts Medical Society.