engleski

Differences in serum levels of soluble Fas and FasL in patients with human immunodeficiency virus, human herpesvirus type 8 and herpes simplex virus type 2 infections

Objectives: Fas mediated apoptosis is considered to be an important T cells depletion mechanism in HIV-infection. Soluble Fas (sFas) prevents apoptosis by inhibiting Fas binding with Fas ligand or soluble FasL (sFasL). We investigated possible differences in sFas and sFasL serum levels in HIV patients with herpes simplex type 2 (HSV-2) and human herpesvirus type 8 (HHV-8) coinfection. Methods: Levels of sFas and sFasL were measured by EIA in 136 HIV patients sera divided according to HHV-8 and HSV-2 antibody status. Four HIV patients groups were studied: 1) without HHV-8 and HSV-2 (n=48), 2) with HHV-8 and HSV-2 (n=21), 3) with only HSV-2 (n=61), 4) with only HHV-8 (n=6). HIV-negative persons (n=39) without HHV-8 and HSV-2 and HIV-negative with HSV- 2 antibodies (Ab) (n=20) served as controls. In statistical analyses we used the Kruskal-Wallis and Mann-Whitney-Wilcoxon tests. The Bonferroni correction was applied for pairwise comparisons. Results: The median concentrations of sFas and sFasL were: 589.3 pg/ml and 47.8 pg/ml in HIV patients without HHV-8 and HSV-2 ; 892.3 pg/ml and 72.2 pg/ml in HIV patients with HHV-8 and HSV-2 ; 717.6 pg/ml and 40.9 pg/ml in HIV patients with only HSV-2 ; 1010.6 pg/ml and 70.9 pg/ml in HIV patients with only HHV-8 ; 678.9 pg/ml and 61.4 pg/ml in HIV-negative controls ; 695.2 pg/ml and 59.9 pg/ml in HIV-negative controls with HSV-2. Higher sFas and sFasL levels were found in HIV patients with HHV-8 and HSV-2 compared to HIV patients without HHV-8 and HSV-2 Ab (P<0.001 ; P=0.001, respectively) and also compared to HIV patients with only HSV-2 Ab (P 0.034 ; P<0.001, respectively). Higher sFas was also found in HIV patients with HHV-8 and HSV-2 Ab compared to HIV- negative controls without HHV-8 and HSV-2 Ab (P=0.046). HIV patients with only HHV-8 Ab had higher sFas than HIV patients without HHV-8 and HSV-2 Ab (P=0.006). Lower sFasL levels were found in HIV patients with only HSV-2 Ab than in HIV- negative controls with and without HSV-2 Ab (P=0.001 ; P<0.001, respectively). Conclusion: Our results suggest that HHV-8 and HSV-2 infections may mediate apoptosis signalling molecules sFas and sFasL. The increased sFas concentrations found in HIV patients with positive HHV-8 and HSV-2 Ab suggest suppression of Fas mediated apoptosis. Our findings need to be confirmed by additional in vitro data and further studies are necessary to define the clinical significance of these findings.

HIV; soluble Fas and FasL; HHV8; HCV type 2

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