J.A. Girón-González

Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis

The objectives of this work were the analysis of the functional characteristics of circulating monocytes and T lymphocytes in patients with liver cirrhosis, and evaluation of the relationship with an increased exposure to antigens due to bacterial translocation. Forty patients with liver cirrhosis (20 with compensated cirrhosis and 20 with ascitic decompensation) and 20 healthy control subjects were studied. Bacterial translocation was evaluated by serum levels of lipopolysaccharide binding protein (LBP). Macrophage activation was studied by CD40 antigen expression. T lymphocytes were analysed for activation (CD25+, CD122+), effector function (CD8+CD45RO+CD57+), apoptosis (CD95+) and regulatory abilities, either by analysis of the membrane expression of co‐stimulatory molecules CD80, CD86 and CD28, or by quantification of regulatory T cells CD4+CD25highforkhead box P3 (FoxP3). The percentage of activated monocytes and T lymphocytes in patients was increased significantly. The proportions of effector senescent cells and of those near to apoptosis were also significantly higher. With respect to these proportions, there were no significant differences between patients in function of the presence or absence of decompensation or in function of the increased or normal values of LBP. Conversely, those patients with elevated levels of LBP presented a significantly higher frequency of regulatory T cells than those with normal levels. In conclusion, patients with liver cirrhosis showed an intensive activation state with a higher percentage of cells committed to activation‐induced death, even in non‐advanced stages. It is possible that bacterial permeability and endotoxaemia contribute to the expansion of those lymphocyte populations implicated in the prevention of a more severe antigen‐induced immunopathology.

Serial analysis of serum and ascitic fluid levels of soluble adhesion molecules and chemokines in patients with spontaneous bacterial peritonitis.

The aim of this work was the evaluation of serum and ascitic fluid levels of chemokines (IL‐8, growth‐regulated oncogene (Gro‐α), and monocyte chemotactic protein‐1 (MCP‐1)), and of soluble adhesion molecules (P‐selectin, E‐selectin, l‐selectin, intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1)) in patients with spontaneous bacterial peritonitis (SBP). These compounds were serially analysed in serum and ascitic fluid by ELISA in patients with SBP (nu2003=u200320), non‐infected cirrhotic controls (nu2003=u200312), and healthy controls (nu2003=u200315). Infected and non‐infected cirrhotic patients showed significantly higher serum levels of adhesion molecules. SBP was associated with significantly higher serum and ascitic fluid levels of IL‐8, Gro‐α and ICAM‐1 and with ascitic fluid concentrations of MCP‐1. Significantly elevated serum levels of both ICAM‐1 and VCAM‐1 were detected in patient non‐survivors after SBP. Thus, higher ascitic fluid levels of chemokines could be implicated in the peritoneal infiltrate in patients with SBP. Prognostic significance can be attributed to serum levels of ICAM‐1 and VCAM‐1 in these patients.

Efficacy of Directly Observed Treatment of HIV Infection: Experience in AIDS Welfare Homes

With the objective of analyzing the efficacy of directly observed treatment (DOT) of HIV infection in the management of severely immunodepressed patients, this method was examined in individuals cared for in two social welfare facilities for HIV-infected persons and compared to self-administered therapy in outpatients. Forty-seven patients with registered HIV infection, stage C, were assigned to DOT for 9 months, the majority of whom had previously received antiretroviral therapy. A group of 51 HIV-infected outpatients, who attended day clinics attached to the reference hospitals, served as a comparison group. Together with increases in weight (9.2±7.5xa0kg) and Karnofsky scores (16.9±12.2) in the DOT group, a significant improvement of surrogate markers, such as CD4+ T-cell counts (increase in DOT group, 113.4±151.0 cells/µl; control group, −2.8±114.1 cells/µl; P<0.001) and HIV load (decrease in DOT group, −1.7±2.3xa0log10 copies/ml; control group, −0.4±1.5xa0log10 copies/ml; P<0.01) was detected in the DOT group. Morbidity and mortality were similar in both groups. The results indicate that such welfare facilities provide a useful framework not only for social objectives but also for healthcare purposes.

Fiebre Q aguda: riesgo de desarrollo de endocarditis

OBJECTIVESnAssess clinical and serological data as parameters indicative of a possible evolution to endocarditis after an episode of acute Q fever.nnnPATIENTS AND METHODSnRetrospective cohort study of evolution to endocarditis after an acute Q fever episode, analyzing the clinical and serological evolution and the antibiotic treatment administered.nnnRESULTSnEighty patients were recruited, 20% of whom had phase i IgG antibody levels ≥ 1:1024 in the first 3 months. Only 44% of the patients underwent antibiotherapy in the acute phase; only 2 patients underwent extended antibiotherapy. Fifteen percent of the patients underwent an echocardiogram. None of the patients had symptoms suggestive of chronic infection or progressed to endocarditis after a median follow-up of 100 months, regardless of the early increase in phase i IgG antibodies.nnnCONCLUSIONSnThe early increase in phase i IgG antibodies in asymptomatic patients is not associated with progression to endocarditis despite not undergoing prolonged antibiotic treatment.

Peripheral Th17 cells expressing β7 intestinal homing receptor in recent and chronic HIV infections

The objective of this study was to conduct an analysis of peripheral blood Th17 cells with the ability to home to gut mucosa (CD4+Th17+β7+) during recent or chronic human immunodeficiency virus (HIV) infections. The relationship between HIV load and systemic inflammation markers was studied. Twenty‐five patients with recent (n = 10) or chronic (n = 15) untreated HIV infections; 30 treated HIV‐infected patients with undetectable HIV load at the time of inclusion and 30 healthy controls were included. Bacterial translocation markers (16S rDNA), soluble CD14 (sCD14) and interleukin (IL)‐6 monocyte activation parameters, CD4/CD8 ratio and T helper type 17 (Th17) subpopulations [CD4+Th17+ expressing the IL‐23 receptor (IL‐23R) or β7] were analysed at baseline and after 6 and 12 months of anti‐retroviral therapy (ART). 16S rDNA was detected in all patients. Significantly increased serum levels of sCD14 and IL‐6 and a decreased CD4/CD8 ratio were observed in patients. Similar percentages of CD4+IL‐23R+ and CD4+Th17+β7+ cells were observed in healthy controls and patients at baseline. After 12 months of therapy, patients with a recent HIV infection showed significant increases of CD4+IL‐23R+ and CD4+Th17+β7+ cell percentages and a decrease in IL‐6 levels, although 16S rDNA continued to be detectable in all patients. No significant differences were observed in Th17 subpopulations in patients with chronic HIV infection after therapy. Early initiation of ART helps to increase the number of Th17 cells with the ability to home to the intestinal mucosa and to partially restore gut mucosal homeostasis. These results provide a rationale for initiating ART during the acute phase of HIV infection.