Inhibition of Fas/Fas ligand-mediated apoptotic cell death of lymphocytes in vitro by circulating anti-Fas ligand autoantibodies in patients with systemic lupus erythematosus.
Arthritis Rheum
; 41(2): 344-53, 1998 Feb.
Article
em En
| MEDLINE
| ID: mdl-9485093
ABSTRACT
OBJECTIVE:
The Fas/Fas ligand (FasL) system has been assigned a pivotal role in the establishment and maintenance of peripheral tolerance, and mice having defects in the Fas/FasL system are known to develop lupus-like symptoms. However, it remains unclear whether the Fas/FasL system is involved in the pathogenesis of systemic lupus erythematosus (SLE) in humans. This study examined whether there are circulating anti-FasL autoantibodies in the peripheral blood of patients with SLE that would interfere with Fas/FasL-mediated apoptosis.METHODS:
Anti-FasL autoantibodies were detected by Western blot analysis using the recombinant extracellular domain of human FasL as the antigen. Apoptosis of Fas-expressing Jurkat cells, induced by recombinant soluble FasL (sFasL) in the presence of anti-FasL autoantibodies, was assessed by DNA staining with propidium iodide, followed by flow cytometric analysis. Apoptosis of Jurkat cells by cell-bound FasL was assessed by 2-color analysis, involving TUNEL staining with fluorescein isothiocyanate-dUTP and phycoerythrin-labeled anti-CD3 monoclonal antibodies.RESULTS:
Among the 21 patients with SLE, 7 had IgG-isotype anti-FasL autoantibodies in their circulating blood. In addition, these autoantibodies inhibited both sFasL-mediated and cell-bound FasL-mediated apoptosis of Fas-expressing Jurkat cells. Thus, it is plausible that anti-FasL autoantibodies in patients with SLE disturb the establishment and maintenance of peripheral tolerance in vivo by inhibiting the Fas/FasL-mediated elimination of autoreactive lymphocytes.CONCLUSION:
These results suggest that anti-FasL autoantibodies that inhibit Fas/FasL-mediated apoptosis are involved, at least in part, in immune abnormalities and may possibly be involved in the pathogenesis of SLE.
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Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Glicoproteínas de Membrana
/
Linfócitos
/
Apoptose
/
Receptor fas
/
Lúpus Eritematoso Sistêmico
Limite:
Adolescent
/
Adult
/
Animals
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Arthritis Rheum
Ano de publicação:
1998
Tipo de documento:
Article