Evaluation of serum levels and significance of soluble CD40 ligand in screening patients with hepatitis C virus-related hepatocellular carcinoma

The study's objective was to evaluate the clinical significance of sCD40L in HCV- associated hepatocellular carcinoma [HCV-HCC] patients. Sera concentration of circulating sCD40L and IL-10 were assayed using ELISA in 30 HCV positive patients with HCC, 30 HCV-positive patients with liver cirrhosis and 30 age-matched healthy volunteers with negative anti-HCV-Ab as a control group. Serum sCD40Lshowed statistically-significant high levels in HCV-HCC patients compared to HCV-cirrhotic patients and normal controls [P < 0.001]. Serum sCD40L had higher diagnostic value in HCC patients compared with serum AFP. High sensitivity and specificity of sCD40L was observed compared to AFP [90%, 86.7% and 83% and 80% respectively]. Significant positive correlation was detected between serum sCD40L and IL-10[r = 0.85 P < 0.001], AFP [r = 0.62 P < 0.05] and tumour staging [r = 0.5 P < 0.05]. The study concluded that sCD40L is a valuable diagnostic tool in early diagnosis and screening for HCV and HCC as well as routine follow up of HCV cirrhosis patients. Assessment of serum IL-10 levels in HCV patients may provide a possible predictive marker for disease progression

Correlations between Serum Inflammation Factors and Left Ventricular Remodeling in Acute ST Segment Elevation Myocardial Infarction

PURPOSE: To investigate the changes and correlations of the serum inflammation factors levels and left ventricular (LV) structure and function in patients with acute ST segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS: A prospective study was performed on 70 STEMI patients and 70 control subjects. Serum levels of interleukin-6 (IL-6), soluble CD40 ligand (sCD40L), metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by sandwich enzyme-linked immunosorbent assay (ELISA), and cardiac structure and function were assessed by echocardiography at admission and 3-year follow-up. RESULTS: We found that the levels of serum IL-6, sCD40L and MMP-9 increased steadily among control subjects, remote myocardial infarction and acute STEMI patients, and the level of TIMP-1 elevated remarkly at 3-year follow-up visit in STEMI. The admission level of serum MMP-9 positively correlated with LV end-diastolic and end-diastole volume (r=0.294, p=0.022; r=0.269, p=0.036, respectively), and TIMP-1 positively correlated with E/A ratio (r=0.278, p=0.044) at 3-year follow-up. CONCLUSION: The study indicates that admission levels of serum MMP-9 and TIMP-1 closely correlated with left ventricular structure and function, which may be involved in the process of post-infarction remodeling of myocardium.

Correlations between Coronary Plaque Tissue Composition Assessed by Virtual Histology and Blood Levels of Biomarkers for Coronary Artery Disease

PURPOSE: We investigated correlations of coronary plaque composition determined by virtual histology (VH) intravascular ultrasound (IVUS) and blood levels of biomarkers that represent the vulnerability of coronary plaques. MATERIALS AND METHODS: Pre- and postprocedural blood levels of high sensitivity C-reactive protein, soluble CD40 ligand (sCD40L), matrix metalloproteinase-9, and neopterin were measured in 70 patients with stable angina (SA) or unstable angina (UA) who were undergoing percutaneous coronary intervention (PCI) for single lesions. We evaluated the data for correlations between these biomarkers and necrotic core contents in PCI target lesions analyzed by VH. RESULTS: Clinical characteristics, IVUS, VH, and biomarker blood levels were not different between the SA and the UA group except for more frequent previous statin use (52.3% vs. 23.1%, p=0.017) and lower remodeling index in the SA group (0.98+/-0.09 vs. 1.10+/-0.070, p<0.001). Among the biomarkers evaluated, only pre-PCI neopterin level showed a weakly significant correlation with the absolute volume of the necrotic core (r=0.320, p=0.008). Pre- and post-PCI blood levels of sCD40L (r=0.220, p=0.072; r=0.231, p=0.062) and post-PCI blood level of neopterin (r=0.238, p=0.051) showed trends toward weakly positive correlations with the absolute volume of necrotic core. CONCLUSION: We found a weakly positive correlation between the pre-PCI neopterin level and necrotic core volume in the PCI-target lesion. The clinical implications of our findings need to be investigated in further studies.

Study of the role of CD40 / CD40-L interaction in the pathogenesis of rheumatoid arthritis [RA]

CD40/CD40 ligand [CD4O/CD4O-L] interaction has pleiotropic effects in a variety of cells and biological processes including immune response. Within the immune system, these molecules represent a critical link between its humoral and cellular arms. Numerous autoimmune diseases are associated with CD40/CD40-L interaction. CD40 is a cell surface receptor that belongs to the tumor necrosis factor-receptor [TNF-R] family, and that was first identified and functionally characterized on B- lymphocytes. CD40 ligand [CD40-L] or [CD154], a member of the TNF superfamily, is a cell membrane molecule expressed on activated CD4+ T-lymphocytes. Therefore, it is now thought that CD40/CD40-L interactions play a more important role in autoimmune disease regulation. The aim of the present work was to measure the level of surface expression of CD40-L and CD40 on PB lymphocytes of rheumatoid arthritis [RA] patients and to correlate it with clinical and laboratory data and with disease activity. To achieve this goal, 30 patients with RA [Group I] who were further subdivided into group IA [15 patients with active RA] and group IB [15 patients with inactive RA], in addition to 20 healthy control volunteers [group II] were studied. All studied groups were subjected to routine laboratory investigations including, complete blood count [CBC], ESR, C-reactive protein [CRP], rheumatoid factor [RF] measured by latex test and by Rose-Waaler test. Surface CD40-L and CD40 expression on lymphocytes was measured by flowcytometry on peripheral blood [PB] of all studied groups. Statistical analysis of the results of the present study showed that surface expression of CD40-L on PB T-lymphocytes was significantly higher in RA compared to the control group. Among RA patients surface expression of CD40-L was significantly higher in active RA patients compared to inactive patients. As regards CD40 expression on PB, no statistical significance was observed among the studied groups. Therefore increased expression of CD40-L on PB T-lymphocytes could be regarded as a marker of disease activity in RA patients and to drive the activation of autoreactive beta-lymphocytes in the disease. These findings are particularly useful for clarifying the pathogenic process in RA patients and for developing a therapeutic approach that blocks pathogenic cytokine and antibody production

Serum levels of soluble CD40 ligand in patients with chronic and acute coronary syndromes and its relation to angiographic extent of coronary arterial narrowing

The aim of this study was to determine serum levels of soluble CD4O ligand [sCD4OL] in patients with chronic and acute coronary syndromes [ACS] and to assess the relation between sCD4OL levels and extent of coronary arterial narrowing in patients with ACS. Acute coronary events commonly result from thrombosis triggered by disruption of an atherosclerotic plaque. Recent studies have localized the receptor CD4O and its ligand in human atheroma. The CD4OL on activated T cells and platelets, by inducing the expression of matrix- degrading proteinases and of tissue factor procoagulant, may contribute to the triggering of acute coronary events. To study the role of CD4OL-CD4O interaction in coronary artery disease, we analyzed serum levels of sCD4OL in the peripheral blood from 10 patients with stable angina [SA]. 26 patients with unstable angina [UA], 22 patients with acute ST-segment elevation myocardial infarction [Ml] and 20 healthy controls by enzyme-linked immunosorbent assay [ELISA]. Coronary angiograms of all the VA patients and 18 Ml patients were reviewed to determine the culprit vessel [CV], CV complexity score [CVCS] [a score of I is given to a simple stenosis, 2: complex stenosis, 3: intracoronary thrombus, 4: total occlusion], type of CV lesion [A, B or C according to the lesion morphology] and vessel score [number of vessels with >/= 50% diameter stenosis]. Both patients with UA and Ml showed significantly higher levels of serum sCD4OL compared to patients with SA and controls; particularly high levels occurred in patients with UA [F ratio 34.9, p <0.001]. No statistically significant difference in sCD4OL levels was noted between VA and Ml patients or between SA patients and controls. Levels of sCD4OL did not show any significant correlation to peak CK. CK-MB in Ml patients or troponin T serum levels in UA patients. Levels of sCD4OL did not also show any significant correlation to CVCS, type of CV lesion or vesset score in VA or Ml patients. This study shows enhanced levels of sCD4OL levels in patients with UA and MI patients suggesting that CD4OL-CD4O interaction plays a pathogenic role in the triggering of ACS. Serum levels of sCD4OL could not however, predict the angiographic extent of coronary arterial narrowing