Telomerase activity and apoptosis genes as parameters of lymphocyte aging in down syndrome patients

It is hypothesized that Down syndrome [DS] patients are associated with abnormalities of the immune system. Accordingly, this study was conducted to measure replicative aging and apoptosis in lymphocytes, which play an important role in the immune system, before and after being biostimulated with He:Ne laser. Replicative aging was measured in terms of telomerase activity, and ETS-2 gene relative expression. Apoptosis was measured in terms of DNA fragmentation and apoptosis genes [Fas, FasL and Bax] and antiapoptotic Bcl-2 protein. Results showed that Telomerase activity, ETS-2 mRNA expression, plasma DNA fragmentation, Fas and FasL were significantly higher among DS patients compared to controls: Telomerase activity [1.5 +/- 0.5 vs. 0.9 +/- 0.4, p < 0.001]; ETS2 mRNA expression [0.6 +/- 0.1 vs. 0.43 +/- 0.04,p < 0.0001]; plasma DNA fragmentation [0.45% +/- 0.12 vs. 0.2% +/- 0.1, p < 0.0001]; Fas protein [5.3 +/- 1.2 vs. 2.3 +/- 0.2, p < 0.0001]; FasL mRNA relative expression [0.37 +/- 0.05 vs. 0.24 +/- 0.01, p < 0.001]; Bax mRNA relative expression [0.9 +/- 0.1 vs. 0.5 +/- 0.1, p < 0.00001]. Bcl-2 protein was significantly low in DS patients compared to controls [8.6 +/- 1.3 vs. 10 +/- 2.1, p < 0.01]. He:Ne laser biostimulation applied to evaluate lymphocytes' response significantly increased the former parameters in DS patients compared to their level before irradiation, except for Bcl-2, which was significantly decreased. In conclusion: increased telomerase activity associated with increased activity and overexpression of ETS-2 on chromosome 21 in DS patients may contribute to the increased rate of early senescence in circulating lymphocytes, which consequently contributes to the abnormalities of the immune system observed in DS. Increased apoptosis is due to increased oxidative stress, which induces an increase in the apoptotic genes Bax, Fas and FasL accompanied by a decrease in the antiapoptotic gene Bcl-2

Expression of FAS protein [CD95] and fas ligand in liver tissue of patients with HCV-induced chronic liver disease and its correlation with the disease progression

This study evaluated hepatic expression of both Fas and Fas ligand [FasL] in patients with hepatitis c virus [HCV]-induced chronic liver disease and its correlation with the histopathological activity and laboratory parameters as an early predictor of advancement of the disease. The selected patients were [39] males and [21] females, their ages ranged from [20-67years] with a mean of 43.5 +/- 4.5 years, as well as [10] subjects [normal individuals] serving as a control group. They were [7] males and [3] females, their age ranged from [26-53 years] with a mean of 39.5 +/- 7.3 years. Patients were grouped as [1] Chronic hepatitis [CH] group including [30] patients with chronic viral hepatitis C. [2] Liver cirrhosis [LC] group including [30] patients with post hepatitis C cirrhosis. Liver biopsy was done for all subjects using an automated 18-gauge true cut needle. Sections were stained with Haematoxylin and Eosin for histopathological diagnosis and with Maisson and Trichrome for assessment of fibrosis. Unstained paraffin sections from each case were subjected for immuno-histochemical procedures using indirect immunoflourescence technique for detection of apoptotic hepatic and lymphocytic cells using monoclonal antibodies. Semiquantitative analysis of the pattern and distribution of the Fas antigen and Fas Ligand as indicators for hepatic apoptosis was studied and assessed

S-Fas Urinary Excretion Helps to Predict the Immunosuppressive Treatment Outcomes in Patients with Proliferative Primary Glomerulonephritis

Deregulation of soluble apoptosis stimulating fragment (sFas) plays an important role in glomerulonephritis (GN). The study assed the influence of immunosuppressive treatment on serum and urine sFas in patients with proliferative (PGN) and non-proliferative (NPGN) GN, and evaluated the potential of sFas measurements in predicting outcomes. Eighty-four patients with GN (45 males and 39 females) were included. Serum concentration (ng/mL) and urinary excretion (ng/mg of urinary creatinine) of sFas were measured before and after the treatment. After 12 months of therapy with steroids and cyclophosphamide, patients were divided into two subgroups according to the treatment results: Responders (R) and Non-Responders (NR). The sFas urinary excretion was reduced after treatment in both PGN and NPGN (from 17.12 +/- 15 to 5.3 +/- 4.2, P = 0.008 and from 10.11 +/- 6.1 to 3.4 +/- 3.0, P = 0.039; respectively) whereas the sFas serum concentration remained unchanged. In PGN, pre-treatment urinary sFas concentration was significantly lower in the Responders than in Non-Responders (2.3 +/- 3.1 vs 19.4 +/- 14.1, P = 0.003), and was lower still than in both R (P = 0.044) and NR (P = 0.042) subgroups with NPGN. The immunosuppressive treatment reduced sFas urinary excretion in proliferative and non-proliferative GN and results suggest that the lower urinary sFas may be linked with favorable therapy outcomes in patients with PGN.

Detection of B cell lymphoma 2, tumor protein 53, and FAS gene transcripts in blood cells of patients with breast cancer.

Background: Proteins encoded by FAS, BCL-2 and TP53 genes are major regulators of cellular survival and apoptosis. Results of recent investigations show remarkable biological features of these factors, which propose their role in the course of cancer. Therefore, it is plausible to test whether transcripts of these genes could be detected in the peripheral blood cells of patients with breast cancer. Materials and Methods: Real-time polymerase chain reaction assay was performed to detect FAS, BCL-2, and TP53 gene transcripts in the peripheral blood samples of 50 women with histologically confirmed infiltrative ductal carcinoma of the breast. Gene expression of patients was compared with 40 healthy women without history of malignancies or autoimmune disorders. Results: The relative overexpression of BCL-2 in the blood cells from patients of early stages (I and II), nonmetastatic and low-grade tumors compared with healthy individuals, was shown by measuring the gene transcript. Similarly, 3-4-fold higher expression of FAS was found in those patients. The measurement of TP53 transcripts also showed higher levels of gene expression in patients compared with healthy controls. BCL-2 gene expression showed a significant correlation with FAS, while such a correlation was not observed between BCL-2 and TP53 . Conclusion: It seems tumor cells overexpress BCL-2 to inhibit apoptosis and guarantee their cell survival. As a physiologic response, FAS and TP53 could be upregulated to suppress tumors. However, these pathways at early stages of disease may be inadequate and cause progressive malignancy.

Correlation between serum levels of soluble fas [CD95/Apo-1] with disease activity in systemic lupus erythematosus patients in Khorasan, Iran

Soluble Fas [sFas] is a marker of apoptosis that appears to increase in the serum of systemic lupus erythematosus patients and may have a correlation with disease activity. The exact role of sFas in apoptosis is not clear. The purpose of this study is to assess the correlation between serum levels of soluble Fas [Apo/1-CD95] and the activity of systemic lupus erythematosus. Our study was performed on 114 systemic lupus erythematosus patients who were compared with 50 randomly selected sex, age and race-matched healthy controls. Disease activity was defined according to the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI-2K]. All physical exams and laboratory parameters were collected to determine the SLEDAI. sFas levels were determined using a commercially available ELISA kit. There was a significant difference between serum levels of sFas in the case and control groups [P=0.001]. A significant correlation coefficient existed between the sFas and SLEDAI2K variables [P=0.001, r=0.494]. Significant statistical difference was found between serum levels of sFas in the active and inactive phases of disease according to SLEDAI< 9 or >10, [P=0.002]. The sFas levels were 270 - 300 pg/mL for SLEDAI<9 and 355-502 pg/mL for SLEDAI>10, with a confidence interval of 95%. This study shows a significant elevation of sFas levels in the sera of systemic lupus erythematosus patients with active disease; therefore it can be used as an appropriate marker for evaluation of disease activity

Apoptosis of peripheral blood cytotoxic T lymphocytes in chronic hepatitis C virus infection: relation to disease severity and response to therapy

More than 80% of HCV-infected individuals develop chronic disease, which can progress to liver cirrhosis and hepatocellular carcinoma. T cell-mediated protection against HCV depends on constantly activated effector CD8+ T cells that control emergence, spread and expansion of the virus. Why these cells fail to contain HCV replication in 70-80% of the individuals who develop persistent viremia is not clear. Fas receptors [APO-1 or CD95] and the Fas ligand system [Fas/FasL] have been implicated in the induction of apoptosis which is related with the pathogenesis of hepatitis C. Was to assess the expression of CD95 [Fas/APO-1] [as an apoptotic marker] on peripheral blood cytotoxic T lymphocytes from patients with chronic HCV infection and to correlate this with disease severity in the liver, response to antiviral therapy and extrahepatic autoimmune manifestations. Thirty patients with evidence of chronic HCV infection and 10 healthy age and sex matched volunteers with negative HCV antibodies sera serving as controls were enrolled into the present study. Our patients were classified into two main groups according to antiviral therapy, Group A: They were 17 patients not receiving treatment and Group B: They were 13 patients who received antiviral therapy for 24 weeks. Group A patients were further subdivided according to the presence or absence of extrahepatic manifestations into two groups: Group I: They were 11 patients not receiving therapy and had no extrahepatic manifestations. Group II: They were 6 patients not receiving therapy and had extrahepatic manifestations. Group I patients were also subdivided according to the necroinflammatory score in liver biopsy into three groups with: Mild, moderate and severe disease activity. They were also subdivided as regard fibrosis stage in liver biopsy into groups with: Moderate and severe fibrosis. Group B patients were further subdivided according to their response to antiviral therapy into: Group III: 6 patients received therapy and were non responders and Group IV: 7 patients received therapy and showed good response. After detailed history taking and thorough clinical examination, the following investigations were done: CBC, AST and ALT, serum cryoglobulins [for patients with extrahepatic disease] and flowcytometric estimation of the percentage of apoptotic peripheral blood cytotoxic T lymphocytes [CD8+CD95+] and non apoptotic cytotoxic T lymphocytes [CD8+ CD95-]. Current liver biopsy was performed in patients of Group I and examined histopathologically. There was highly statistically significant difference between HCV patients and controls as regard ALT, percentage of apoptotic cytotoxic T lymphocytes [CD8+ CD95+] and non apoptotic cytotoxic T lymphocytes [CD8+ CD95-] [p<0.001]. There was statistically significant difference between patients of Group I, II, III, IV and controls in percentage of CD8+CD95+ and CD8+CD95- cells. Comparison between Group I and II revealed non significant difference in percentage of CD8+CD95+ and CD8+CD95- cells or in percentage of CD8-CD95+ cells [apoptotic non cytotoxic T] [p>0.05]. Comparison between Group III and IV revealed statistically significant difference in percentage of CD8+CD95+ and CD8+CD95- cells [p<0.05]. In Group I the percentage of CD8+CD95+ tended to correlate with activity index of liver biopsy but significantly correlated with serum ALT in Group III. In Group II significant positive correlation between percentage of CD8+CD95+ and AST with tendency toward correlation with ALT was found. Also percentage of CD8+CD95+ correlated with purpura and arthritis but not with cryoglobulinemia. Percentage of CD8+CD95+ showed non statistically significant correlation except with serum prothrombin time in group IV. There was increase in the percentage of CD8+CD95+ cells in higher grade of necroin-flamatory activity and in higher stage of fibrosis in liver biopsy in group I. Our findings support the suggestion of major role of peripheral blood CD8+ T cells in elimination of HCV and suggest that cellular immune response plays a key role not only in viral elimination, but also in liver pathology associated with HCV-infection. Monitoring apoptosis of CD8+ T cells by measuring FAS expression is useful in follow-up of antiviral response in these patients. Finally, Fas/FasL pathway is critical in persistent HCV infection in humans and represents a potential target for restoring function of exhausted HCV-specific CTLs

Investigation of apoptotic markers among human immunodeficiency virus (HIV-1) infected individuals.

BACKGROUND & OBJECTIVES: Apoptosis causes a decline in the counts of uninfected bystander CD4+ T cells in HIV infection. The rate of disease progression of HIV infection is considered to be faster in the developing countries. The present study was carried out to investigate certain markers for apoptosis in immunopathogensis of disease in HIV infected south Indian population. METHODS: Soluble Fas (sFas) antigen and Fas ligand levels in plasma samples from 39 antiretroviral treatment naïve patients was estimated and compared with T cell subsets and HIV-1 viral load. RESULTS: The mean sFas antigen levels among controls and the CDC A, B and C clinical stages were 2.77, 3.08, 3.26 and 3.28 ng /ml respectively, higher though not significantly among HIV-1 infected individuals compared to controls. The mean sFas ligand levels in CDC A, B and C stages were 0.138, 0.125 and 0.117 ng/ml respectively were higher (P<0.001) than controls (0.073 ng/ml) and positively correlated with total lymphocyte % (r=0.43, P =0.007). sFas antigen levels were negatively correlated with total WBC count (r=-0.34, P=0.04), CD4% (r=-0.4, P=0.01) and CD4:CD8 ratio (r=-0.37, P=0.02). There was an increase in plasma levels of sFas antigen and Fas ligand over time in asymptomatics. INTERPRETATION & CONCLUSION: The high levels of sFas antigen and Fas ligand seen in HIV infected individuals suggest increased activation and apoptosis of T cells, due to constant stimulation of the immune system by inter-current infections of HIV infected individuals in south India.

Cell-mediated immunity in recent-onset type 1 diabetic children

The ability to suppress an immune response makes regulatory T-cells [T-reg] an attractive candidate as a novel therapeutic agent for treating autoimmune diseases. The mechanisms involved in maintenance of peripheral tolerance include a specialized subset of regulatory-T-cells [T-reg] within the T-cell population. The CD4[+] CD25[+] T-cells may be, important in modulating the risk for autoimmunity. Auto-reactive cytotoxic-cells recognize peptide epitopes displayed on the beta cells surface in the context of HLA class] molecules. A population of CD8[+] regulatory T-cells characterized by expression of CD25 and FOXP3 have been identified and induced in the human peripheral blood cells. The regulatory activity of these cells is on autologous, antigen-reactive CD4[+] T-cells in a cell contact-dependent manner. These findings provide an evidence for a new mechanism for induction of immune regulation in human. This study was aiming to assess the cellular immune parameters including the percentage of CD4[+], CD8[+], CD4[+]/CD8[+] ratio,CD4[+]CD25[+], CD8[+] CD25[+] lymphocytes, which may have its application in developing immune therapy based tools for halting disease progression. This study was conducted on 20 children of recent onset type 1 diabetes [disease duration 0.05] between the two groups. A significant inverse correlation was found between CD4[+] CD25[+] T-cells and HbA1c percentage among patients group [p<0.05].Also a significant difference in the percentage of CD4[+] CD25[+] T-cells was found when patients with HbA1c<8%w ere compared to those with HbA1c >/= 8% [the latter group had significantly lower percentage of CD4[+] CD8[+] T-cells]. Type 1 diabetes is characterised at its onset by a lowered percentage of CD8[+] and CD8[+] CD25[+] T-cells in peripheral blood, a normal percentage of CD4[+] and CD4[+] CD25[+] T-cells. There may be an inverse correlation between percentage of CD4[+] CD25[+] T-cells at disease onset and HbA1c level after three months. These data support the hypothesis that a defect in function or deficiency in number of T-regulatory cells may affect the pathogenesis of type 1 diabetes

Alteration in circulating soluble Fas level in Toxoplasma seropositive pregnant women

The role of sFas in human toxoplasmosis was designed, included 23 pregnant women serologically positive for anti-Toxoplasma antibodies, and ten sero-negative pregnant females constituted the control group. Antibody titer was assessed by indirect haemagglutination test. The presence of specific IgM antibodies was determined by comparing antibody titer before and after serum treatment with 2-mercaptoethanol. sFas was quantified in sera of cases and controls by enzyme linked immunosorbent assay. Antibody titers ranged from 1/160 to 1/640. All cases were negative for specific IgM antibodies indicating that they had passed the acute stage of infection Statistical analysis revealed significant elevation in sFas level in cases compared to controls. The sFas role in establishment of a stable host parasite interaction in toxoplasmosis was discussed

Renal and ocular complications and it's relationship to glycemic control, CD95 and soluble fas [s Fas] in type 1 diabetes mellitus [DM]

Type 1 diabetes mellitus [DM] is an autoimmune disease that results from the destruction of insulin-secreting pancreatic islet beta cells by autoreactive cells and their mediators. The aim of this study was to analyze the expression of Fas receptors [CD[95]] on T and B lymphocytes from patients with type 1 DM and to assess the role of soluble Fas [s-Fas] in Fas mediated apoptosis of T and B lymphocytes, and to assess the role of glycemic control in renal and ocular complications. This study was carried out on three groups: Group I: consist of 16 patients with type 1 DM. Their age ranged from [11-18] years old with mean duration of illness 6 +/- 4 months. Group II: consist of 16 patients with long standing type 1 DM, their age ranged from 10 19 years old, with mean duration of illness 30 +/- 10 months. Group III: consist of 16 healthy persons their age ranged from 10.5 -19.5 years old. Results can be summarized as follows: The incidence of positive microalbuminuria as well as incidence of retinopathy were significantly higher in group II [long standing DM] than newly diagnosed case [group I]. Microalbuminuric patients had significantly higher HbA[1]C than others. Newly diagnosed cases [group I] as well as [group II] long standing DM type 1 had significantly higher percentage of T and B lymphocyte bearing Fas receptors [CD[95]] as compared to control group. Mean plasma level of s-Fas showed a significant increase in both DM groups as compared to control group. There is no significant difference in the percentage of lymphocytes expressing CD95, and plasma s-Fas levels when compared microalbuminuric to normoalbuminuric patients. There was positive correlation between HbA[1]C and microalbuminuria in diabetic patients, there was positive correlation between HBA[1]C and% of lymphocyte expressing the Fas receptors [CD95]. In both diabetic groups, positive correlation was found between HbA[1]C and s-Fas in DM type 1. Also, positive correlation was found between% of cells expressing CD[95] and s-Fas. In conclusion, the study of the possible role of apoptosis of autoreactive lymphocytes and its regulation, in the pathogenesis of type 1 DM may provide new therapeutic tools for the prevention of the disease. Further analysis, is necessary to finally settle this point, to elucidate the roles played by distinct immunological pathway in diabetes pathogenesis, this can lead to more effective and targeted therapies for the disease. Poor glycemic control is an essential initiating factor of defective apoptosis in type 1DM

Role of apoptosis and fas expression in premature rupture of membranes

To examine the degree of apoptosis [programmed cell death] and to evaluate Fas [a cell surface receptor] receptor expressmon in human fetal membranes associated with premature rupture of membrane [PROM] as compared with normal pregnancies. Fetal membranes from 60 pregnancies were included in the study. Forty of 60 pregnancies had PROM. Twenty pregnancies with intact membranes served as controls. Chorioamniotic membrane biopsies were taken from the rupture site and periphery of the rupture site. In the control group, membrane biopsies were taken from the artificial rupture site, cervical pole of the membranes close1to the edge of the placenta. Samples were fixed in neutral buffered formalin and processed for paraffin embedded tissue. Sections were prepared for morphometric measurement and immunohistochemistry evaluation using Fas receptor expression. Patients with PROM showed reduction of the chorionic thickness [P<0.001] while decidual thickness showed non-significant difference versus control group [p>0.13]. Apoptotic cells were detected predominantly in the chorioaznniotic membrane, including the trophoblastic layer, and decidua. There was a statistically significant difference between the apoptotis [represented by Fas expression] of the PROM and control groups in both the rupture and peripheral sites [P<0.05]. Of the 40 cases that could be evaluated after immunohistochemical staining, Fas expression of the amniotic epithelial cells was observed in 40% of control cases and in 60% of cases with PROM. Fas expression was noticed to be increased in association with PROM group [p=0.0001] as well as with reduction of the chorionic thickness [p=0.001]. Negative Fas expression was noticed to be associated with increased thickness of the. chorionic layer. Fas receptor mediated apoptosis-has a role.in premature rupture of fetal membranes

Immunohistochemical detection of fas expression and Bcl2 in liver tissues of patients with chronic liver disease

Apoptosis is a type of cell death that occurs in chronic hepatitis. It has been suggested to be mediated through Fas antigen. Bcl[2] gene is involved in the regulation of programmed cell death by providing a survival advantage to rapidly proliferating cells. This work aims to study Fas expression [as apoptotic marker] and Bcl, in different chronic liver disease and to correlate-these findings with the etiological causes, severity of the disease and with the progress of the pathology. This study was carried on 77 cases with chronic liver diseases and 5 control cases. Patients were admitted diagnosed and managed in Tropical Medicine Department in El Zahraa University Hospital. All cases were subjected to full history taking, full clinical examination and laboratory investigation in the form of complete blood picture, liver function tests, kidney function tests, hepatitis markers upper gastrointestinal endoscopy, sigmoidoscopy and abdominal ultrasonography. Liver biopsy was taken and examined histopathologically also for the presence of expression of Fas and BcL[2]. Patients were classified into 4 groups I: pure schistosamal infection, group II: pure chronic hepatitis C infection, group III: mixed schistosomal and viral hepatitis, and group IV: hepatocellular carcinoma. Our results showed Fas expression in the GI, II, III, IV in [50% +/- 2.5, 72% +/- 3.2, 85% +/- 4.8, 35.2 +/- 3.2] at the hepatocytes while the expression at the Kupifer cells were [35.2 +/- 11.2, 60.4 +/- 12.2, 65.4 +/- 10, 83 +/- 2.2]. On the other hand, it was expressed at the portal tracts in [25.2 +/- 8, 50.1 +/- 5.2, 60.2 +/- 2.4, 15.4 +/- 2] in the studied groups respectively. This expression increased significantly in all liver tissues of chronic liver diseases when compared with the control group and it was markedly elevated at the Gill [group of mixed infection] also it is increased with the severity of disease either the necro-inflammatory activity or the fibrosis staging. While the Bcl[2] expression was found to be-increased at the malignant tissues [502 +/- 4.2] than other lesions [20.2 +/- 2.4, 35.5 +/- 4.5, 40.8 +/- 2.7] also in cirrhotic patients than the non-cirrhotic patients. There was significant increased difference between the groups and the group of control, this expression also correlated with the presence of Fas expression significantly [r=0.333, p<0.01]. Also Bcl[2], expression was found to be significantly increased with the necroinfiammatory state, fibrosis staging and also with the malignant differentiation. So, from these results, we concluded that apoptosis plays an important role in the pathogenesis of chronic liver disease either due to chronic hepatitis C virus infection, schistosomiasis and malignancy. Process of apoptosis may be related to immune mediated system and active inflammation of the liver. This may explain the high Fas expression in cases of mixed schistosomiasis and chronic hepatitis C infection. Also the antiapoptotic regulator Bcl2 may contribute to viral persistence and progression of liver disease in chronic hepatitis C. As well this expression may be used as a prognostic indicators of hepatocellular carcinoma in cirrhotic and hepatitis patients

Peripheral blood lymphocytes apoptosis in juvenile idopathic arthritis: relation to disease activity and type of onset

Abnormalities in the mechanisms regulating apoptosis may have a role in the pathogenesis of autoimmune disorders. The aim of this study was to evaluate the incidence of apoptosis of peripheral blood [PB] lymphocytes in children with juvenile idiopathic arthritis [JIA] and correlating it with CD95 [APO-1/Fas] antigen expression and serum levels of sFas and interleukin-15 [IL-15] in different types of onset and activity of the disease. PB lymphocytes apoptotic index [AI], CD95 [APO-1/Fas] antigen expression, serum levels of sFas and IL-15 were detected in 30 cases of JIA and 20 healthy controls. Results were correlated with the type of onset, activity of the disease and acute phase indicators [ESR, CRP]. The mean values of AI, CD95, sFas and IL-15 were higher in children with JIA than in healthy controls. Significant difference was only found for AI especially with systemic type of onset and high activity. Also the levels of IL-15 increased with activity especially in the systemic type. Moreover, AI showed a significant positive correlation with ESR and CRP but not with IL-15, CD95, or sFas. AI of lymphocytes was high in systemic onset JIA and in active disease and correlated with ESR and CRP, but not with IL-15, CD95 expression or serum sFas

Serum soluble fas in patients with pre-eclampsia and the syndrome of hemolytic anemia, elevated liver enzymes and low platelet count [HELLP] syndrome

Pre-eclampsia carries statistically significant perinatal risk to both the mother and the fetus. HELLP syndrome is a complex disease process that is probably mediated by numerous factors. It appears that the immune system may play a role in its pathogenesis.Apoptosis or programmed cell death is a physiological process for normal development and reproductive function. It has been found to be involved in different inflammatory and immune disorders. The Fas-Fas ligand system is one of the best-studied death systems that can mediate apoptosis. Soluble Fas [sFas], a protein related to the tumor necrosis factor receptor family, protects cells from Fas mediated apoptosis by binding to Fas ligand preventing it from stimulating Fas receptor on the cell membranes and consequently inducing apoptosis. The objective of this work is to assess whether serum levels of soluble Fas, are altered in cases of pre-eclampsia and HELLP syndrome. Results showed that serum soluble Fas was statistically higher in patients with HELLP syndrome compared to those with mild or severe pre-eclampsia with values of 12.7 +/- 1.1 u/ml, 7.1 +/- 1.1 u/ml and 8.1 +/- 1.3 respectively. Moreover, it was higher than normal control subjects with mean serum value of 6.1 +/- 0.4 u/ml

Apoptosis in type 2 diabetic patients with micro vascular complications

Type 2 diabetes mellitus results from an inadequate adaptation of the functional pancreatic beta cell mass in the face of insulin resistance. Apoptosis is programmed cell death or cell suicide, it is an energy-requiring process that involves de novo protein synthesis. Apoptotic mechanisms could explain insulin deficiency through a reduction in absolute beta cell mass. This study was conducted on 49 patients with type 2 diabetes mellitus from Internal Medicine Department, Kasr- El Aini hospital. They were classified into group A [10 patients] without micro vascular complications, group B [39 patients]with micro vascular complication [peripheral neuropathy, retinopathy and nephropathy] and 10 healthy persons served as control group[group C].All subjects were subjected to full Clinical assessment and routine laboratory investigations, 24 hours urinary albumin, ECG, fundus examination and quantitative assay of proapoptotic markers [Fas, FasL, and Bcl2 proteins] There was significant correlation behveen fasting blood glucose and Fas, FasL, and Bcl2 [P value

Fas antigen in serum and liver tissue of patients with chronic hepatitis C

Fas [APO-1/CD95], a member of the tumor necrosis factor receptor Family, can mediate apoptosis when engaged by its ligand or by anti-Fas antibody. Fas is upregulated on the surface of hepatocytes in patients with a variety of liver pathologies, including hepatitis, alcoholic cirrhosis, and acute liver failure. Moreover, expression of Fas ligand is substantially upregulated, in areas of lymphocytic infiltration, in liver diseases, suggesting Fas/FasL interactions may mediate liver damage in humans. The purpose of this study was to evaluate the relationship of serum soluble Fas [sFas] levels and hepatic Fas antigen expression with the degree of hepatic inflammatory activity in patients with chronic hepatitis C infection. The effect of concomitant schistosomiasis, as an endemic liver disease in Egypt, on serum and liver Fas expression was also studied. Serum sFas levels were measured by enzyme-linked immunosorbant assay in 69 chronic hepatitis C patients; 16 of them were under 18 years and compared with those in normal volunteers, and patients with chronic HBV infection. The results of serum tests were compared with ALT levels. HCV-RNA titer, histological inflammatory activity, and Fas expression in liver biopsies. The effect of combined HCV infection and schistosomal infestation on serum sFas and tissue Fas expression was also studied. Serum sFas and tissue Fas expression were then evaluated with each components of histological inflammatory activity scoring system [modified Knodell's HAI]. Serum sFas levels in chronic hepatitis C patients were significantly higher than those in normal volunteers [p<0.001]. They showed no difference from those in patients with chronic HBV infection [p>0.05]. Hepatic schistosomiasis didn't affect serum sFas levels or tissue expression of Fas antigen in chronic hepatitis C patients. Histologically, serum sFas levels showed strong correlation with tissue Fas expression [p<0.001] and with the degree of hepatic inflammatory activity [p<0.01]. Likewise, tissue Fas expression correlated with the degree of histological inflammatory activity [p<0.05]. Moreover, positive correlation was found between serum sFas and tissue Fas expression and the degree of interface hepatitis [piecemeal necrosis] in chronic hepatitis C patients with mild [p<0.01] and moderate and severe activity [p<0.05]. However, no correlation was observed between serum sFas and serum ALT levels. Also, no correlation was observed between HCV-RNA titer and sFas levels or tissue Fas expression. Our findings suggest that serum sFas levels may reflect the expression of Fas antigen on hepatocytes and the severity of liver inflammation in chronic hepatitis C and may be used as a serological indicator of histological inflammatory activity. They also support the concept that immune-mediated apoptosis may play a crucial role in the pathogenesis of chronic hepatitis C. Hepatic schistosomiasis seems to have no impact on serum sFas levels or hepatic tissue Fas expression

CD[95] as an early and sensitive marker of neonatal sepsis and disease outcome

This study was carried out on 33 neonates. They were classified into 2 groups: the first group included 18 septic neonates [9 males and 9 females] of these 11 were fullterm and 7 were perterm. The second group included 15 healthy neonates as a control group [7 males and 8 females] of these 10 were full term and 5 were preterm. All cases and controls were subjected to thorough history, clinical examination, laboratory investigation for both groups included: complete blood picture, total and differential leucocytic count, erythrocyte sedimentation rate [ESR], c-reactive protein [CRP], blood culture in septic cases and Fas /Apo 1 / CD[95]. The level of CD[95] is significantly elevated in septic full term and septic preterm compared to normal full term and normal preterm respectively [both P<0.0001]. Comparing CD[95] levels in septic neonates according to the severity of infection there was significant difference between cases who recovered and those who died [P<0.05]. There was no significant correlation between the levels of CD[95] in septic cases and the causative organism. Comparing CD[95] with other laboratory results, there was significant negative correlation between CD[95] levels and platelet count, significant positive correlation with total leucocytic count in septic full term and negative correlation in septic premature. There was also positive correlation between CD[95] level and CRP. In conclusion, soluble CD[95] can be used as an early and sensitive marker in diagnosis of neonatal sepsis

Serum levels of soluble CD95 in patients with systemic lupus erythematosus

The present study was carried out on 30 patients with systemic lupus erythematosus [SLE] and ten apparently healthy individuals as a control group.Systemic lupus erythematosus activity index [SLEDAI] was applied to all patients. Anti-double stranded DNA antibodies [Anti-dsDNA Abs.], interleukin-18 [IL-18] and soluble CD95 [Apo-1/Fas] were determined in the sera of all studied subjects. The mean +/-SD SLEDAI in all patients was 15.25+/- 6.76 . The anti-dsDNA antibodies was positive in all studied patients [mean +/- SD 264.36 +/- 114.85 IU/ml]. Serum IL-18 showed significant elevation in SLE patients as compared to the control group [Mean +/-SD 246.13+/- 114.32I U/ml vs. 45.5 +/- 7.32 IU/ml; p < 0.001]. Serum Soluble CD95 [sCD95] showed significant increase in all SLE patients as compared to the control group [Mean+/-SD 648+/-116.96 pg/ml vs. 270+/-50.24 pg/ml; p < 0.001]. Serum sCD95 also showed significant rise in SLE patients with moderate activity as compared to those with mild activity [Mean +/- SD 629.16+/- 72.54 pg/ml vs. 535 +/-35.97 pg/ml; p<0.05]. The serum level of sCD95 in SLE cases with severe activity showed significant increase when compared to those with moderate activity [Mean+/-SD 797.5 +/- 41.66 pg/ml vs. 629.16 +/- 72.54 pg/ml; p <0.001]. Anti-dsDNA antibodies showed significant positive correlation with SLEDAI [r=0.772; p<0.01]. IL-18 also showed a significant positive correlation with the SLEDAI [r=0.670; p<0.01]. Soluble CD95 showed significant positive correlation with SLDAI [r=0.865; p<0.01], with anti-dsDNA antibodies [r=0.775; p<0.01] and with IL-18 [r =0.722; p<0.01]. From these results it was concluded that serum sCD95 is increased in patients with systemic lupus erythematosus and it is correlated with anti-dsDNA antibodies, with IL-18 and with the disease activity, so it can be useful marker of disease activity for proper management and follow up of SLE patients

Serum soluble fas in children with idiopathic dilated cardiomyopathy

The present study aimed to evaluate the role of serum soluble Fas [sFas] "APO-l receptor", as an inhibitor of apoptosis [programmed cell death] in children patients suffering from idiopathic dilated cardiomyopathy [IDCM] and its association to New York Heart Association [NYHA] Functional class. The study included 20 children patients aged 5-13 years, suffering from IDCM and 20 age and sex matched control subjects. Serum level of sFas was measured by enzyme linked immunosorbent assay [ELIZA] which showed that sFas is increased significantly with increased NYHA functional class. However, serum levels of sFas were similar in normal subjects and patients with functional class I, but there were significant differences between functional classes II, III and IV. Serum levels of sFas were significantly higher in patients with an elevated Pulmonary Capillary Wedge Pressure [PCWP] > 18 mm Hg than in those with values <18 mm Hg. Six months later, all patients were re-evaluated for their functional class and serum sFas levels. Serum levels of sFas decreased in four patients with clinical improvement but were similar in patients with no change in functional class. The increase in sFas may play an important role in the pathophysiologic mechanisms of IDCM in children

Serum levels of soluble Fas in children with congestive heart failure

This study was done to investigate the role of apoptosis [programmed cell death] in children with congestive heart failure [CHF]. Serum levels of soluble Fas [sFas], an inhibitor of apoptosis was estimated in 30 children with CHF, 10 due to rheumatic heart disease [RHD], 10 due to congenital ventricular septal defect [VSD] and 10 due to idiopathic dilated cardiomyopathy [IDCM]. The children included were 20 males and 10 females, aged between 7 to 14 years. The diagnosis was based on thorough clinical and echo-Doppler examinations. They were classified according to the New York Heart Association [NYHA] functional class based on their clinical characteristics. Ten normal healthy children with matched age and sex served as a control group. Our results showed that there was a significant increase in serum levels of sFas in children with CHF as compared to the control group. There was a significant positive correlation between serum levels of sFas and NYHA functional class. Serum levels of sFas were correlated with certain echo-Doppler parameters that reflect the severity of CHF resulting in a significant positive correlation with pulmonary wedge pressure [PWP] and a significant negative correlation with ejection fraction [EF]. The increase in serum levels of sFas was related to the severity of CHF independently of the underlying cardiac disease. Serum levels of sFas tended to decrease significantly in children with CHF who underwent clinical improvement but not significantly changed in the stable cases during the six months follow up. There was no significant difference in serum levels of sFas between the survivors and those children who died. In conclusion: serum levels of sFas, an inhibitor of apoptosis may play an important role in the pathophysiologic mechanisms of CHF in children