Regulation of peripheral blood and synovial fluid lymphocyte apoptosis in juvenile idiopathic arthritis.
OBJECTIVE
Complex regulatory mechanisms are involved in the induction of apoptosis. Their impairment may play a role in the pathogenesis of several autoimmune diseases. Recently, we have described higher incidences of spontaneous apoptosis of peripheral blood (PB) lymphocytes in children with juvenile idiopathic arthritis (JIA). This study aimed to evaluate the regulatory mechanisms that may be responsible for this phenomenon.


METHODS
Thirty-four JIA children were examined and compared with 20 healthy children of similar ages. Expression of regulatory proteins p53, Bax and Bcl-2 in lymphocytes isolated from PB and synovial fluid (SF) was assessed. Serum and SF levels of interleukin-15 (IL-15) were also evaluated.


RESULTS
The study showed significantly decreased Bcl-2 expression in JIA PB lymphocytes, compared to both healthy control (p = 0.03) and JIA SF lymphocytes (p = 0.005). There were no significant differences found in Bax expression between groups or compartments examined. However, the Bax/Bcl-2 ratio was nearly two-fold higher in PB lymphocytes than in SF of JIA patients (p = 0.001). p53 expression in PB lymphocytes from both JIA and control children did not statistically differ. In JIA, however, p53 was significantly higher in PB than SF lymphocytes (p = 0.016). IL-15 levels were about 20-fold higher in JIA SF than in serum from either JIA or healthy children (p < 0.0001).


CONCLUSIONS
The results suggest that a higher incidence of apoptosis of PB lymphocytes observed in JIA may be associated with down-regulation of Bcl-2, rather than with changes in expression of Bax and p53. In contrast, the low p53 expression and elevated IL-15 appear to provide mechanisms responsible for suppression of apoptosis in SF cells from JIA patients.
Smolewska
E
E
Department of Paediatric Cardiology, Institute of Pediatrics, Medical University of Lodz, Poland. piotr_smolewski@wp.pl
Brózik
H
H
Smolewski
P
P
Darzynkiewicz
Z
Z
Stańczyk
J
J
D000293:Adolescent; D017209:Apoptosis / Q000502:physiology*; D001171:Arthritis, Juvenile / Q000209:etiology* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019409:Interleukin-15 / Q000032:analysis; D008297:Male; D011336:Probability; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013582:Synovial Fluid / Q000166:cytology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism*
D015415:Biomarkers; D019409:Interleukin-15; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53