Activation-induced cell death and Fas-induced apoptosis in patients with systemic or pauciarticular juvenile idiopathic arthritis.
OBJECTIVE
To investigate the functionality of the Fas-induced apoptotic pathway in peripheral blood mononuclear cells (PBMC) from patients with systemic or pauciarticular juvenile idiopathic arthritis (JIA).


METHODS
PBMC from 12 patients with systemic and 6 with pauciarticular JIA were activated with anti-CD3 and rhIL-2 and then incubated in the presence or absence of the anti-Fas MoAb CH11 inducing activation of the Fas apoptotic pathway. Apoptosis was evaluated by flow cytometry and fluorescence microscopy.


RESULTS
The percentage of apoptotic cells following triggering of Fas did not differ between patients with systemic JIA (12.5 +/- 9.5%) or pauciarticular JIA (18.7 +/- 8.9%) and controls (16.1 +/- 6.8%). Evaluation of activation-induced cell death (AICD) in the absence of exogenous triggering of Fas showed that 44% (8/18) of the patients with JIA, compared to none of the controls (0/16), had a percentage of apoptotic cells higher than the mean + 2 SD of controls. The increased AICD was neutralized by the addition of an anti-TNF-alpha antibody.


CONCLUSIONS
Patients with systemic or pauciarticular JIA do not show a defect in the Fas-dependent apoptotic pathway of T cells. The increased AICD present in some patients with JIA appears to be at least in part related to the inflammatory cytokine TNF-alpha.
Pignatti
P
P
Clinica Pediatrica, IRCCS Policlinico San Matteo, Pavia, Italy.
Massa
M
M
Travaglino
P
P
Meazza
C
C
Martini
A
A
De Benedetti
F
F
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D001171:Arthritis, Juvenile / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor