Using immunohistochemistry, we studied the
IgG subclass distribution of the anti-Hu antibody in serum, nervous system, and
tumor of patients with anti-Hu-associated
paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN). The nervous system was also examined for deposits of
complement and the distribution and type of inflammatory cells.
IgG1 and
IgG3 were the predominant isotypes of the anti-Hu
IgG in serum, nervous system, and
tumor. A few patients also had anti-Hu
IgG2, but this isotype was not consistently present in all the regions of the nervous system studied. There was no correlation between
neurologic symptoms and specific anti-Hu isotype, nor was there evidence that different anti-Hu isotypes recognized specific brain regions. Although
IgG1 and
IgG3 can activate
complement, only weak
complement reactivity was found, and that only in a few areas of the nervous system. This finding, in addition to the absence of natural killer (NK) cells, suggested that
complement-mediated toxicity and antibody-dependent cell cytotoxicity mediated by NK cells are not pathogenic in PEM/PSN. Inflammatory infiltrates included CD19+ (B cells) and CD4+ (helper/inducer) cells in the perivascular spaces, and lymphocytes bearing CD8+CD11b- markers (cytotoxic T cells) in the interstitial spaces. Infiltrates of EBM11+ (monocyte/macrophage) cells were identified in the perivascular spaces (macrophage phenotype) and in those interstitial regions (microglial phenotype) with severe pathologic changes. The ability of the
IgG1 and
IgG3 isotypes to bind
Fc receptors may have played a role in the recruitment of these monocyte/macrophage cells.(ABSTRACT TRUNCATED AT 250 WORDS)