RESUMEN
Background: CTLA-4 [CD152] encodes cytotoxic T lymphocyte-associated antigen-4, a cell-surface molecule providing a negative signal for T-cell activation. CTLA-4/B7 is the most important costimulation-signaling pathway that regulates T cell responses and plays a critical role in maintenance and breakdown of selftolerance, and hence in susceptibility to autoimmune diseases
Objective: The aim of this study was to investigate and evaluate the expression of CTLA-4 on peripheral blood T-lymphocytes [PBTL] in children with systemic lupus erythematosus [SLE] in relation to clinical features; disease activity and severity
Methods: From December 2006 to August 2007, 32 pediatric patients [30 girls, 2 boys] fulfilled at least four of the 1997 revised criteria for the classification of SLE were enrolled in this study. Expression of CTLA-4 on freshly isolated PBTL was assayed by flow cytometry in all SLE patients during activity and remission in addition to 32 age- and sex-matched children serving as controls. Results were expressed as percentage of PBTL cells expressing surface CTLA-4 molecule in comparison to isotype-matched controls. CTLA-4+PBTL% were correlated with some SLE disease activity and severity variables
Results: CTLA-4 expression on freshly isolated PBTL was significantly higher in SLE patients during disease activity [median = 12; mean +/- SD = 10.45 +/- 8.3%] than controls [median = 4; mean +/- SD = 3.34 +/- 3.1%; p < 0.0001]. The patients' values were statistically comparable during quiescence [median = 14; mean +/- SD = 15.02 +/- 7.1%; p > 0.05] and activity. Among SLE patients, the median and mean +/- SD of CTLA-4+PBTL % of children with lupus nephritis was significantly higher than those without nephritis [15; 13.56 +/- 10.4% versus 10; 9.51 +/- 9.1%; p < 0.01]. CTLA-4 expression could be related to lupus severity but there was no correlation with disease activity. A positive correlation could be elicited between CTLA-4+PBTL% during lupus activity and the corresponding values during remission. CTLA-4+PBTL% correlated positively with the anti-dsDNA autoantibodies titers, serum creatinine, and 24 hours urinary protein excretion. On the other side, the percentages correlated inversely with the estimated creatinine clearance and serum C3 and C4 levels. CTLA-4 expression did not vary according to therapy
Conclusion: CTLA-4 surface expression on PBTL in SLE children was up regulated irrespective of lupus activity. The over expression was related to lupus severity and might have a significant role in the pathogenesis of lupus nephritis and cerebritis
RESUMEN
Background: Systemic Lupus Erythematosus [SLE] remains a potentially disabling, life-threatening and overall challenging disease. The role of T cell derived cytokine production in SLE is poorly understood. It was hypothesized that interferon-gamma [IFN-gamma] and interleukin-10 [IL-10] are important cytokines in the pathogenesis of SLE. Understanding their possible role in the pathogenesis might lead to the development of new, more targeted drugs to manage this intractable disease
Objectives: To study IFN-gamma and IL-10 mRNA expression in peripheral blood mononuclear cells [PBMCs] in patients with SLE, correlating them with the disease activity score as measured by Systemic Lupus Activity Measures [SLAM] score; in an attempt to throw light on their possible role in the pathogenesis of the disease
Subjects: Forty selected patients with SLE [15 with active disease as group I, and 25 in remission as group II] and 15 healthy controls with matched ages and sex were studied
Methods: Using reverse transcriptase-polymerase chain reaction [RT-PCR], IFN-gamma and IL-10 mRNA expression in PBMCs was measured in both patients and controls
Results: This study showed a significant [p<0.05] decrease in haemoglobin and lymphocyte percents in patients than in controls and a significant [p<0.05] increase in expression of both IFN-gamma and IL-10 mRNA in PBMCs of patients than controls. The IFN-gamma expression was higher in group I of patients than those in group II, however, this difference did not attain statistical significance [p>0.05]. There was also no statistically significant [p>0.05] difference between both groups of patients as regards IL-10 expression. A significant positive correlation was detected between IFN-gamma expression and SLAM score [r=0.36, p=0.02], also between IL-10 expression and duration of illness [r=0.175, p=0.018], and between IFN-gamma expression and IL-10 expression [r=0.85, p<0.001] but both IFN-gamma and IL-10 expression were negatively [insignificant] correlated with cortisone intake [r=0.22, p=0.06 and r=0.12, p=0.5, respectively]
Conclusion: Results of this work support the hypothesis that IFN-gamma and IL-10 play a key role in the immunopathogenesis of SLE and suggests that IFN-gamma might be considered as an important independent marker of disease activity