Association of serum soluble Fas concentrations and mortality of septic patients

Serum soluble Fas (sFas) levels are associated with erythropoietin (Epo) hyporesponsiveness in patients with chronic kidney disease (CKD). Whether sFas could predict the need for erythropoiesis-stimulating agent (ESA) usage and its influence in erythropoiesis remain unclear. We evaluated the relation between sFas and ESA therapy in patients with CKD with anemia and its effect on erythropoiesis in vitro. First, we performed a retrospective cohort study with 77 anemic patients with nondialysis CKD. We performed in vitro experiments to investigate whether sFas could interfere with the behavior of hematopoietic stem cells (HSCs). HSCs were isolated from umbilical cord blood and incubated with recombinant sFas protein in a dose-dependent manner. Serum sFas positively correlated with Epo levels ( r = 0.30, P = 0.001) but negatively with hemoglobin ( r = −0.55, P < 0.001) and glomerular filtration rate ( r = −0.58, P < 0.001) in patients with CKD at baseline. Elevated sFas serum levels (4,316 ± 897 vs. 2,776 ± 749, P < 0.001) with lower estimated glomerular filtration rate (26.2 ± 10.1 vs. 33.5 ± 14.3, P = 0.01) and reduced hemoglobin concentration (11.1 ± 0.9 vs. 12.5 ± 1.2, P < 0.001) were identified in patients who required ESA therapy compared with patients with non-ESA. Afterward, we detected that the sFas level was slight correlated with a necessity of ESA therapy in patients with nondialysis CKD and anemia. In vitro assays demonstrated that the erythroid progenitor cell frequency negatively correlated with sFas concentration ( r = −0.72, P < 0.001). There was decreased erythroid colony formation in vitro when CD34+ HSCs were incubated with a higher concentration of sFas protein (1.56 ± 0.29, 4.33 ± 0.53, P < 0.001). Our findings suggest that sFas is a potential predictor for ESA therapy in patients with nondialysis CKD and that elevated sFas could affect erythropoiesis in vitro.

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Circulating progenitor cells in patients with atrial fibrillation and their relation with serum markers of inflammation and angiogenesis

Thrombosis and Haemostasis ◽

10.1160/th10-01-0024 ◽

2010 ◽

Vol 104 (08) ◽

pp. 327-334 ◽

Cited By ~ 4

Author(s):

Andrew Blann ◽

Timothy Watson ◽

Eduard Shantsila ◽

Gregory Lip

Keyword(s):

Atrial Fibrillation ◽

Sinus Rhythm ◽

Progenitor Cells ◽

Cell Population ◽

Fas Ligand ◽

Serum Markers ◽

Endothelial Damage ◽

Stepwise Multiple Regression ◽

Soluble Fas ◽

Markers Of Inflammation

Summary The pathophysiological inter-relationships and underlying ‘drivers’ of a prothrombotic state in atrial fibrillation (AF) are complex but may include endothelial abnormalities. Circulating progenitor cells (CPCs) have been recently described as a cell population that may promote repair of endothelial damage. We hypothesised abnormalities in this cell population, alongside abnormal markers of endothelial damage/dysfunction (von Willebrand factor, soluble E-selectin), apoptosis (soluble Fas, soluble Fas ligand), angiogenesis (vascular endothelial growth factor) and inflammation (interleukin-6) in 135 consecutive AF patients (14 with lone AF), who were compared to 33 ‘disease controls’ and 13 healthy controls. We also explored whether restoration of sinus rhythm would alter these indices. No significant differences in research indices were observed between AF and disease controls, apart from soluble Fas levels (p<0.001). Median CPC levels in lone AF were higher compared to ‘non-lone AF’ (that is, AF patients with co-morbidities) [p<0.001], apparently because of difference in age and presence of co-morbidities. There was an increase in CPC counts (p=0.007), but in not other markers following DC cardioversion. CPCs increased significantly in the 17 patients who were successfully cardioverted into sinus rhythm (p=0.003). In a stepwise multiple regression analysis, age (p=0.014), hyperlipidaemia (p=0.001) and use of statins (but not AF) was predictive of CPC counts (p=0.014). In conclusion, AF is unlikely to be independently associated with abnormalities in CPCs. Successful cardioversion is associated with a modest but significant increase in CPCs.

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The −670G>A polymorphism in the FAS gene promoter region influences the susceptibility to systemic sclerosis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2008.088989 ◽

2008 ◽

Vol 68 (4) ◽

pp. 584-590 ◽

Cited By ~ 24

Author(s):

V Liakouli ◽

M Manetti ◽

A Pacini ◽

B Tolusso ◽

C Fatini ◽

...

Keyword(s):

Systemic Sclerosis ◽

Topoisomerase I ◽

Gene Promoter ◽

Serum Levels ◽

Scleroderma Renal Crisis ◽

Genotype Distribution ◽

Healthy Individuals ◽

Soluble Fas ◽

Significant Difference ◽

Pulmonary Arterial

Objective:To evaluate the role of the single-nucleotide polymorphism (SNP) at position −670 in the FAS gene promoter (FAS−670G>A) in influencing the susceptibility, clinical features and severity of systemic sclerosis (SSc).Methods:350 white Italian SSc patients (259 with limited cutaneous SSc (lcSSc) and 91 with diffuse cutaneous SSc (dcSSc)) and 232 healthy individuals were studied. Patients were assessed for the presence of autoantibodies (anticentromere, anti-topoisomerase I (anti-Scl-70) antibodies), interstitial lung disease (ILD), pulmonary arterial hypertension and scleroderma renal crisis. FAS−670G>A SNP was genotyped by PCR restriction fragment length polymorphism assay. Serum levels of soluble FAS (sFAS) were analysed by ELISA.Results:A significant difference in FAS−670 genotype distribution was observed between SSc patients and healthy individuals (p = 0.001). The frequency of the FAS−670A allele was significantly greater in SSc than in controls (p = 0.001). No significant difference in genotype distribution and allele frequencies was observed between lcSSc and dcSSc, although a greater frequency of the FAS−670A allele was found in dcSSc. The FAS−670AA genotype significantly influenced the predisposition to SSc (OR 1.97, 95% CI 1.35 to 2.88, p = 0.001) and to both lcSSc (OR 1.84, 95% CI 1.23 to 2.75, p = 0.003) and dcSSc (OR 2.37, 95% CI 1.41 to 3.99, p = 0.001). FAS−670A allele frequency was greater, although not significantly, in anti-Scl-70 antibody-positive dcSSc and ILD dcSSc. sFAS was significantly higher in patients and controls carrying the FAS−670AA genotype compared with those carrying the FAS−670GG genotype (p = 0.003 in SSc, p = 0.004 in controls).Conclusion:The FAS−670A allele is significantly associated with susceptibility to SSc, suggesting a role for a genetic control of apoptosis in the pathogenesis of the disease.

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