The anti-CD20 monoclonal antibody rituximab has been less successful in treating chronic lymphocytic leukemia (CLL) than lymphoma, possibly due to the lower density of CD20 on B lymphocytes from CLL patients than on those from lymphoma patients. This lowering may result from insufficiency of one of the transcription factors of cd20. Of these, purine-rich box-1 (PU.1) is poorly expressed in CLL. To estimate its weight in CD20 expression, pu.1 cDNA was transfected into CLL B cells and shown to raise the membrane expression of CD20 and to improve the rituximabinduced lysis of transfected cells. Granulocyte macrophage colony-stimulating factor and all-trans-retinoic acids were not involved in the defective expression of PU.1 or the excessive methylation of the pu.1 gene, because 6 of 14 CLL samples tested were normally methylated. This was confirmed by the failure of DNA methyltransferase inhibitors to restore pu.1 transcription in hypermethylated CLL, and, in fact, the expression of PU.1 was down-regulated by excessive expression of the FMS proto-oncogene-like tyrosine kinase 3 (Flt3) receptor. This abnormality is consistent with our finding of elevated levels of Flt3 ligand (FL) in 20 of 23 CLL sera tested. We propose that FL-dependent increased Flt3 signaling prevents the expression of PU.1, which down-regulates that of CD20, and accounts for resistance of leukemic B cells to rituximab-induced lysis.
Background: Physical activity (PA) is an important agent in the prevention of chronic diseases such as obesity. Objectives: To provide preliminary data on PA among school children and to correlate the PA with weight status. Material and Methods: A total of 40 children aged between 8 and 11 years and attending Tunisian schools were recruited. The body composition was determined by using the deuterium oxide dilution technique. PA was determined by the PAQ-C (PA Questionnaire for Older Children). An objective monitoring of PA and sedentary time was achieved by using ActiGraph GT3X + accelerometers. Results: PAQ-C data demonstrate that 20% of the sample had light PA levels and 80% had moderate PA levels. Times spent in sedentary (62.37%) and light (30.80%) activities were higher than that spent in moderate and vigorous (6.83%) activities. Furthermore, almost half of the sample spent more than 60 min per day in moderate-to-vigorous intensity PA (MVPA). The average MVPA was significantly higher in normal weight than overweight and obese groups (67.68 ± 20.98 vs. 49.07 ± 19.09, p = 0.007). The proportion of overweight children who spent more than 60 min per day in MVPA was significantly higher than that of normal-weight (60.9 vs. 29.4%; p = 0.049). Conclusion: This study indicates that half of school children comply with the health-based guidelines for PA and sedentary behavior. Our findings also suggest that obesity was associated with decrease in PA in Tunisian children.
Autoantibodies related to APLS (aCL and aβ2GPI) were present in the majority of patients with PBC, reflecting the ability of these antibodies to engage mediators of damage.
A high frequency of ASCA has been found in coeliac patients. The frequency of ASCA was not statistically different between patients with successful adherence to GFD and healthy controls.
Anti-Saccharomyces cerevisiae antibodies (ASCA) had been known to be specific for Crohn's disease but it has been found in many other autoimmune diseases like systemic lupus erythematosus (SLE). Furthermore, cross-reactive epitopes on β2-glycoprotein I (β2GPI) and Saccharomyces cerevisiae were found in SLE patients. The aims of this study were to evaluate the frequency of ASCA in patients with SLE and to compare it with that of anti-β2GPI antibodies (aβ2GPI). Sera of 116 patients with SLE were analyzed in this retrospective study. All patients fulfilled at least 4 criteria of the 1997 American College of Rheumatology updated criteria for the classification of SLE. Sera of 160 blood donors were included as normal controls. ASCA IgA and IgG and aβ2GPI antibodies were determined by enzyme-linked immunosorbent assays. The frequency of ASCA (IgG and/or IgA) was significantly higher in SLE patients than in control group (31.9 vs. 3.7 %, p < 10(-6)). ASCA IgG and ASCA IgA were more frequent in SLE patients than in control group (29.3 vs. 3.1 %, p < 10(-6) and 12.1 vs. 0.6 %, p = 10(-4), respectively). The mean level of ASCA IgG was higher than that of ASCA IgA (9.5 vs. 6.4 U/ml) but the difference was not statistically significant. The frequencies of aβ2GPI (IgG and/or IgA) and aβ2GPI IgA were significantly higher than those of ASCA (IgG and/or IgA) and ASCA IgA (54.3 vs. 31.9 %, p = 5 × 10(-4) and 50.9 vs. 12.1 %, p < 10(-6), respectively). Increased ASCA IgG was observed in patients with SLE, suggesting a role of environmental stimuli in its pathogenesis.
Onset of the disease above the age of 65 years is unusual. This study was undertaken to determine retrospectively the clinical and laboratory features in SLE patients aged over 65 years. It is a retrospective study about 18 elderly patients with SLE out of 342 diagnosed between 1994 and 2009 in the center of Tunisia. All patients had at least 4 of 11 revised ACR criteria of SLE. The frequency of SLE in the elderly was 5.3%. The median age was 70 years (range 66 and 78 years). The sex ratio F/M was 5. The most frequent clinical signs were anemia (83.3%), arthralgia (55.5%), arthritis (38.9%), and malar rash (33.3%). The proteinuria and the neuropsychiatric troubles were present in 27.8% of cases. The pericarditis was present in 16.7% of cases. Antibodies to double stranded DNA (anti-dsDNA) were detected in 66.7%, anti-nucleosome in 50%, anti-SSA and anti-RNP in 27.8%, anti-Sm in 22%, and anti-SSB in 11%. Elderly patients with SLE exhibit distinct clinical and biological manifestations from the classic form. Thus, greater attention should be given for this particular subgroup of SLE patients to avoid delays in diagnosis or misdiagnosis.
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