Immunological markers after long-term treatment interruption in chronically HIV-1 infected patients with CD4 cell count above 400 x 10(6) cells/l.

OBJECTIVE: To analyse immunological markers associated with CD4+ lymphocyte T-cell count (CD4+) evolution during 12-month follow-up after treatment discontinuation. METHOD: Prospective observational study of chronically HIV-1 infected patients with CD4+ above 400 x 10(6) cells/l. RESULTS: CD4+ changes took place in two phases: an initial rapid decrease in the first month (-142 x 10(6) cells/l on average), followed by a slow decline (-17 x 10(6) cells/l on average) The second slope of CD4+ decline was not correlated with the first and only baseline plasma HIV RNA was associated with it. The decline in CD4+ during the first month was steeper in patients with higher CD4+ and weaker plasma HIV RNA baseline levels. Moreover, the decline was less pronounced (P < 10(-4)) in patients with CD4+ nadir above 350 x 10(6) cells/l (-65 x 10(6) cells/l per month) in comparison with those below 350 x 10(6) cells/l (-200 x 10(6) cells/l per month). A high number of dendritic cells (DCs) whatever the type was associated with high CD4+ at the time of treatment interruption and its steeper decline over the first month. Moreover, the myeloid DC level was stable whereas the lymphoid DC count, which tended to decrease in association with decrease in CD4+, was negatively correlated with the HIV RNA load slope. CONCLUSIONS: The results support the use of the CD4+ nadir to predict the CD4+ dynamic after treatment interruption and consideration of the CD4+ count after 1-month of interruption merely reflects the 12-month level of CD4+. Although DCs seem to be associated with the CD4+ dynamic, the benefit of monitoring them has still to be defined

Modulation of interferon-[alpha] secretion by activated platelets in systemic lupus erythematosus.

Type I interferons play a key role in systemic lupus erythematosus (SLE) pathogenesis as an &#x22;IFN signature&#x22; is found in the majority of patients with active SLE. Immune complexes are internalized by plasmacytoid dendritic cells (DC) via Fc-[gamma] ReceptorIIA, reach the endosomal compartment and activate IFN-[alpha] secretion through TLR7/9-dependent pathways. Naturally occurring differences in expression of the TLR7/9 gene as well as factors that modulate TLR7/9 expression, including CD154 could therefore contribute to SLE pathogenesis. Although its origin is not elucidated CD154 is hyperexpressed in SLE patients, and is important for the differentiation of autoantibody-secreting cells. We hypothesized that platelets which are an abundant source of CD154, and which can mediate proinflammatory effects could be an actor involved in SLE pathogenesis. Platelets from SLE patients are activated _in vivo_ by circulating immune complexes which are abundant in SLE sera, via a CD32-dependent mechanism. Activated platelets formed aggregates with antigen-presenting cells in SLE patients and enhanced interferon-[alpha] secretion induced by immune-complexes stimulated plasmacytoid DCs. Finally, _in vivo_ depletion of platelets and megakaryocytes in NZBxNZW(F1) lupus prone mice improved all parameters assessing disease activity, whereas transfusion of activated platelets worsened the disease course. Altogether, these data identify platelets as a mediator of SLE pathogenesis and a new therapeutical target

Perturbations of the CD8+ T-cell repertoire in CVID patients with complications

AbstractA higher chronic expansion of effector cytotoxic CD8+DR+ T-lymphocytes has been reported in common variable immunodeficiency (CVID) patients with complications such as splenomegaly, autoimmune disease and/or granulomatous disease. In order to document the features associated with this T cell activation involving the CD8+ T-compartment, we examined the diversity of the alpha/beta TCR repertoire of the patient's CD8+ T-lymphocytes using the qualitative analysis of the CDR3 lengths (Immunoscope).Ten CIVD patients were enrolled in this study, four without complications (Group 1), six with complications (Group 2). All patients exhibited non-gaussian altered CDR3 length distributions, albeit to different extent within the different Vβ families. CVID patients with activated CD8+ T-cells show a reduction of their TCR repertoire diversity which is more severe in patients with complications. Viral reactivations such as CMV are suspected to be part of the mechanisms underlying immunosenescence

Altered dendritic cell distribution in patients with common variable immunodeficiency

Recent data suggest a critical role for dendritic cells (DCs) in the generation of immunoglobulin-secreting plasma cells. In the work reported herein, we analyzed the frequency of peripheral blood plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in a cohort of 44 adults with common variable immunodeficiency (CVID) classified according to their CD27 membrane expression status on B cells. A deep alteration in the distribution of DC subsets, especially of pDCs, in the peripheral blood of CVID patients was found. Patients with a reduced number of class-switched CD27(+)IgD(-)IgM(- )memory B cells and patients with granulomatous disease had a dramatic decrease in pDCs (P = 0.00005 and 0.0003 vs controls, respectively) and, to a lesser extent, of mDCs (P = 0.001 and 0.01 vs controls, respectively). In contrast, patients with normal numbers of switched memory B cells had a DC distribution pattern similar to that in controls. Taken together, our results raise the possibility that innate immunity contributes to pathogenesis in CVID

Multi-scale analysis of hypochlorite induced PES/PVP ultrafiltration membranes degradation

In drinking water production plants, the use of oxidants such as sodium hypochlorite during in-place cleanings may impair the membrane integrity and radically impact the ultrafiltration process efficiency, leading to potential contamination of the permeate water with pathogens. This study investigates the effects of hypochlorite exposure on the properties of a commercially available UF hollow fiber. Mechanical performances and water permeability appeared to be greatly affected by the contact with hypochlorite. Monitoring them olecular changes by X-rayphoto electron spectroscopy (XPS), attenuated total reflectance infraredspectroscopy (ATR-IR), size exclusion chromatography (SEC) and VITA-mode atomic forcemicroscopy (VITA-AFM) revealed high stability of the main polymer constituting the membrane (i.e. polyethersulfone (PES)) and very high reactivity of the additive (i.e. poly (N-vinyl pyrrolidone (PVP)) towards immersion in aqueous sodium hypochlorite solution with maximal reaction rate for neutral to slightly basic pH. Correlation of those results unexpectedly leads to the conclusion that the over all membrane properties changes are governed by the additive fate

Virus-Negative Active Lymphocytic Myocarditis Progressing to a Fibrotic Stage

We report a fairly special case of lymphocytic myocarditis progressing to a fibrotic stage, described using multimodality imaging and confirmed on histopathology. This paper presents an uncommon diagnosis with a probable guarded prognosis

Alternative methods to analyse the impact of HIV mutations on virological response to antiviral therapy

<p>Abstract</p> <p>Background</p> <p>Principal component analysis (PCA) and partial least square (PLS) regression may be useful to summarize the HIV genotypic information. Without pre-selection each mutation presented in at least one patient is considered with a different weight. We compared these two strategies with the construction of a usual genotypic score.</p> <p>Methods</p> <p>We used data from the ANRS-CO3 Aquitaine Cohort Zephir sub-study. We used a subset of 87 patients with a complete baseline genotype and plasma HIV-1 RNA available at baseline and at week 12. PCA and PLS components were determined with all mutations that had prevalences >0. For the genotypic score, mutations were selected in two steps: 1) p-value < 0.01 in univariable analysis and prevalences between 10% and 90% and 2) backwards selection procedure based on the Cochran-Armitage Test. The predictive performances were compared by means of the cross-validated area under the receiver operating curve (AUC).</p> <p>Results</p> <p>Virological failure was observed in 46 (53%) patients at week 12. Principal components and PLS components showed a good performance for the prediction of virological response in HIV infected patients. The cross-validated AUCs for the PCA, PLS and genotypic score were 0.880, 0.868 and 0.863, respectively. The strength of the effect of each mutation could be considered through PCA and PLS components. In contrast, each selected mutation contributes with the same weight for the calculation of the genotypic score. Furthermore, PCA and PLS regression helped to describe mutation clusters (e.g. 10, 46, 90).</p> <p>Conclusion</p> <p>In this dataset, PCA and PLS showed a good performance but their predictive ability was not clinically superior to that of the genotypic score.</p

Consultations itératives aux urgences pédiatriques

OBJECTIFS : L'objectif de cette étude est de caractériser les enfants consultant de manière itérative aux urgences pédiatriques dans le but d'émettre des propositions d'éducation et de prise en charge différente de celle des structures d'urgences pour ces enfants. METHODOLOGIE : Il s'agit d'une étude rétrospective. Nous avons sélectionné tous les enfants ayant consulté 5 fois ou plus dans le service des urgences de l'hôpital des enfants de Pellegrin à Bordeaux, durant l'année 2006. Nous avons recherché des facteurs de risques de récurrence en comparant ce groupe avec un groupe témoin puis nous avons réalisé une enquête téléphonique auprès de leur médecin traitant afin d'obtenir des explications colmplémentaires quant à leur récurrence. RESULTATS : Parmi les 157 enfants de ce groupe, 30,6 % sont atteints d'une maladie chronique. Les facteurs de risque de récurrence retrouvés sont l'âge inférieur à 1 an, la proximité du domicile par rapport à l'hôpital, bénéficier de la CMU, l'inquiétude parentale, un contexte socio-économique familial défavorable. Ces enfants consultent plus pour des motifs médicaux que chirurgicaux (dont traumatiques) et sont plus souvent hospitalisés. DISCUSSION : Les facteurs de risque identifiés, nous montrent que pour la majorité des enfants, il existe une mauvaise utilisation des services d'urgences. La mise en évidence de ces facteurs peut nous permettre de repérer ces enfants. Nous pouvons alors tenter d'améliorer leur prise en charge grâce à une meilleure éducation des parents, à la réalisation d'un partenariat avec la médecine libérale et les spécialistes d'organes ainsi qu'en orientant les familles vers des services (sociaux) ou des structures (PMI) plus adaptés que les services d'urgences à la prise en charge de ces enfants.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF