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Autoimmune paraneoplastic cerebellar degeneration

Ultrastructural localization of antibody-binding sites in Purkinje cells

Departments of Neurology (Drs. Rodriguez and O'Neill) and Immunology (Dr. Lennon), Mayo Clinic and Mayo Foundation, and the Mayo Medical School (Ms. Truh), Rochester, MN.

Sera from three of four patients with paraneoplastic cerebellar degeneration (PCD) associated with gynecologic cancer had antibodies that stained the cytoplasm of Purkinje cells in a characteristic discrete and coarsely granular pattern. No such antibodies were found in PCD patients with small cell cancer of the lung, in patients with cerebellar degeneration without cancer, in nonneurologic patients with small cell carcinoma or gynecologic cancer, or in normal subjects. Immunoelectron microscopy revealed that the antibodies of PCD bound to clusters of ribosomes, granular endoplasmic reticulum, and the trans-face of the vesicles of the Golgi complex in Purkinje cells. Immunostaining was localized in orderly arrays of stacked parallel cisternae of the endoplasmic reticulum in the perikaryon and dendritic processes. This pattern suggested that at least one autoantigen of PCD may be a glycoprotein specific for cerebellar tissue that is associated with the endoplasmic reticulum. Some patches of Purkinje plasma membrane also were immunostained.

Address correspondence and reprint requests to Dr. Rodriguez, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

Supported by a grant from the National Cancer Institute (CA-37343). Dr. Rodriguez is the recipient of a Teacher-Investigator Award (NS-849) from the National Institutes of Health and is a John G. Searle Fellow of the Chicago Community Trust.

Presented in part at the sixty-third annual meeting of the American Association of Neuropathologists, Minneapolis, MN, June 1986.

Received July 7, 1987. Accepted for publication in final form January 21, 1988.

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