Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome

Abstract

Paraneoplastic autoimmune disorders are usually regarded as syndromic (for example, paraneoplastic optic neuropathy with CRMP5 antibody, opsoclonus with ANNA-2 (antiRI) antibodies. However, for most paraneoplastic antibodies, the spectrum of clinical manifestations is broader than what was initially described in syndromic patients. This study evaluated coexisting autoantibodies in sera of 553 patients with a neurological presentation and one or more paraneoplastic neuronal nuclear or cytoplasmic autoantibodies: antineuronal nuclear autoantibody type 1 (ANNA-1), ANNA-2, ANNA-3; Purkinje cell cytoplasmic autoantibody type 1 (PCA-1), PCA-2; and CRMP-5-immunoglobulin G or amphiphysin-immunoglobulin G. Except for PCA-1, which occurred alone, 31% of sera had more than one of these autoantibodies. In addition, 25% of sera had neuronal calcium channel (P/Q-type or N-type), potassium channel, ganglionic acetylcholine receptor, muscle acetylcholine receptor, or striational antibodies. The authors conclude that the autoantibody profiles observed in patients with paraneoplastic disorders imply the targeting of multiple onconeural antigens and predict the patient’s neoplasm, but not a specific neurological syndrome. They emphasize that optimal serological evaluation for the detection of autoantibody profiles predictive of cancer requires broad screening for autoantibodies. Indeed, diagnostically important autoantibodies are often missed if a single or limited number of individual antibodies are tested.—Valérie Biousse