Analysis of the IgG subclass distribution and inflammatory infiltrates in patients with anti-Hu-associated paraneoplastic encephalomyelitis.
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)
Jean
W C
WC
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Dalmau
J
J
Ho
A
A
Posner
J B
JB
D000906:Antibodies / Q000032:analysis*; D001426:Bacterial Proteins / Q000276:immunology*; D003165:Complement System Proteins / Q000032:analysis; D004268:DNA-Binding Proteins / Q000276:immunology*; D004679:Encephalomyelitis / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification*; D007150:Immunohistochemistry; D009420:Nervous System / Q000276:immunology; D010257:Paraneoplastic Syndromes / Q000097:blood / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; C040330:histone-like protein HU, bacteria; D003165:Complement System Proteins