Restricted IgG1 subclass of anti-Yo antibodies in paraneoplastic cerebellar degeneration

Paraneoplastic cerebellar degeneration (PCD) occurs as a non-metastatic manifestation of cancer in a small proportion of patients with certain breast or gynaecological tumours, and is characterised by widespread Purkinje cell loss. Antibodies against a Purkinje cell cytoplasmic antigen, called Yo, that is expressed by the tumours, are present in the majority of these patients, but the pathogenic role of the antibodies is not clear. To characterise further the immune response in these cases, 13 anti-Yo positive sera were tested for IgG subclasses by immunohistochemistry and western blotting and, in four cases, PHA-stimulated cytokine secretion by peripheral blood lymphocytes was measured. Surprisingly, anti-Yo antibodies were entirely restricted to the IgG1 subclass, whereas antibodies against the small cell cancer-associated antigen, Hu, were found in all four IgG subclasses. There was a trend towards raised IgG1 levels in the total IgG of the anti-Yo positive patients and, in two, PHA-stimulated peripheral blood lymphocytes secreted raised levels of IFN-gamma. By contrast, in the other two cases tested, raised levels of IL-4 were secreted. Patients with PCD associated with anti-Yo antibodies appear to have strong immune responses that are polarised with respect to the IgG subclass and Th cytokine profiles.