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Volume 3 Supplement 2

21st European Workshop for Rheumatology Research

  • Meeting abstract
  • Open Access

Anti-Fcgamma receptor (FcgammaR) autoantibodies (Ab) delay apoptosis of polymorphonuclear cells (PMN) in systemic autoimmune diseases by inducing the production of G-CSF and GM-CSF

  • 1,
  • 1,
  • 1,
  • 1 and
  • 1
Arthritis Research & Therapy20013 (Suppl 2) :P115

https://doi.org/10.1186/ar284

  • Received: 15 January 2001
  • Published:

Keywords

  • Rheumatoid Arthritis
  • Systemic Lupus Erythematosus
  • Autoimmune Disease
  • Life Span
  • Synovial Fluid

FcγRIIIb is expressed by PMN, and cell-free receptor has also been found circulating in body fluids. We have examined 222 patients with rheumatoid arthritis (RA), systemic lupus erythematosus and primary Sjögren's syndrome and classified anti-FcγR auto-Ab into three groups, based on the results of an indirect immunofluorescence (IIF) test and an ELISA : IIF+/ELISA+ (group A), IIF+/ELISA-(group B) and IIF-/ELISA+ (group C). PMN-binding Ab, i.e. groups A and B, prolonged the survival of PMN by delaying spontaneous apoptosis, and reduced adhesiveness and respiratory burst of these cells. Interestingly, recombinant non-glycosylated and purified glycosylated FcγR produced similar effects as the related auto-Ab.

To delineate the mechanism(s) by which the PMN life span is prolonged, we studied the response of PMN to F(ab')2 fragments of anti-FcγR (CD16) monoclonal Ab. CD16 engagement decreased apoptosis and prevented the up-regulation of β2 integrins, particularly CD11b which is the α chain of complement receptor 3, and CD18 which is its β chain.

The expression of mRNA for G-CSF and GM-CSF was induced. Release of these chimiokines followed CD16 stimulation, suggesting an autocrine involvement of survival factors in the rescue of PMN. The levels of G-CSF and GM-CSF paralleled the amounts of CD16 monoclonal Ab used to stimulate the cells. This set off a partial reduction of caspase 3 activity and was associated with down-expression of Bax. It was shown that anti-G-CSF and anti-GM-CSF Ab inhibited these events, while anti-TNFα was ineffective.

Overall, apoptosis of aged PMN can be modulated by signalling through FcγR, which may occur in patients with PMN-binding auto-Ab. This might be particularly relevant in the synovial fluid of patients with RA.

Authors’ Affiliations

(1)
Brest University Medical School, Brest, France

Copyright

© BioMed Central Ltd 2001

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