PPD-specific IgG1 antibody subclass upregulate tumour necrosis factor expression in PPD-stimulated monocytes: Possible link with disease pathogenesis in tuberculosis

R. Hussain, H. Shiratsuchi, J. J. Ellner, R. S. Wallis

Research output: Contribution to journalArticle

Abstract

Cachexia is a prominent feature of advanced tuberculosis, in association with increased expression of the monokine tumour necrosis factor (TNF)-α. Monocytes, have high affinity receptors (mannose, complement and Fc γ1 and γ111) which mediate antigen uptake and subsequent cytokine activation. Several mycobacterial proteins, including PPD, can stimulate TNF-α secretion from monocytes. However, the role of various receptors in stimulating or regulating TNF-α secretion is still unclear. We have previously shown selective augmentation of opsonic antibodies (IgG1 and IgG3) in tuberculosis patients with advanced pulmonary disease. We now analyse the role of opsonizing antibodies in modulating TNF-α expression in antigen stimulated monocytes. PPD was used as the prototypic myocobacterial antigen to stimulate monocytes from PPD skin test negative donors (n = 7) in the presence of plasma from tuberculosis patients (n = 8), containing known amounts of IgG1 and IgG3 anti-PPD antibodies. TNF-α secretion was enhanced in the presence of TB plasma (4/8) but not in the presence of control plasma. Using Spearman Rank analysis (two-tailed Fisher exact test), a significant correlation (rho = 0.762; P = 0.04) was observed between IgG1 antibodies and enhancement of TNF-α secretion. No significant association was observed with IgG2 (rho = 0.310; P= 0.41), IgG3 (rho = 0.089; P=0.81) or IgG4 (rho=-0.357; P=0.347) subclass antibodies. Absorption of IgG1 with protein 'A' removed the enhancement of TNF-α secretion activity from the plasma samples. Our results therefore indicate that IgG1 antibodies may enhance the chronic release of TNF-α in TB patients with progressive disease and, for the first time, show a direct link between disease pathogenesis and raised antibody levels.

Original languageEnglish (US)
Pages (from-to)449-455
Number of pages7
JournalClinical and Experimental Immunology
Volume119
Issue number3
StatePublished - 2000
Externally publishedYes

Keywords

  • Antibody subclasses
  • Cytokines
  • IgG
  • Monocyte
  • TNF-α
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology

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