Analysis of the IgG subclass distribution and inflammatory infiltrates in patients with anti-Hu-associated paraneoplastic encephalomyelitis Journal Article

Authors: Jean, W. C.; Dalmau, J.; Ho, A.; Posner, J. B.
Article Title: Analysis of the IgG subclass distribution and inflammatory infiltrates in patients with anti-Hu-associated paraneoplastic encephalomyelitis
Abstract: 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 neuronopathy (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+CDllb- 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 pheno-type) 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. We conclude that anti-Hu-associated PEM/PSN is a complex immune disorder in which both cell-mediated and humoral (probably non-CMT and non-ADCC) cytotoxic mechanisms appear to be involved in its pathogenesis. © 1994 American Academy of Neurology.
Keywords: immunohistochemistry; clinical article; controlled study; human tissue; dna-binding proteins; sensory neuropathy; rna binding protein; blood; bacterial proteins; immunoglobulin g; tissue distribution; antibodies; immunoglobulin g1; immunoglobulin g3; inflammatory infiltrate; tumor; paraneoplastic syndrome; immunopathology; complement; nervous system; encephalomyelitis; paraneoplastic syndromes; human; priority journal; article; immunoglobulin g2
Journal Title: Neurology
Volume: 44
Issue: 1
ISSN: 0028-3878
Publisher: Lippincott Williams & Wilkins  
Date Published: 1994-01-01
Start Page: 140
End Page: 147
Language: English
PROVIDER: scopus c2 - 8290049
PUBMED: 8290049
DOI: 10.1212/wnl.44.1.140
Notes: Export Date: 14 January 2019 -- Article -- Source: Scopus
Citation Impact
MSK Authors
  1. Jerome B Posner
    203 Posner
  2. Josep O Dalmau
    101 Dalmau