sCD14 is not a bona-fide biomarker of microbial translocation in HIV-1 infected Africans living in Belgium.

OBJECTIVE: To compare microbial translocation and its biomarkers in HIV-1 infected African and Caucasian patients of the Liege AIDS Reference Center. DESIGN: The study is based on a cross-sectional dataset of HIV-infected patients treated at the Liege AIDS Reference Center. Groups of Caucasian and African patients have been randomly selected in order to be identical for sex, age and duration of treatment. METHODS: sCD14, Lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and routine HIV-follow-up parameters were measured on plasma samples. RESULTS: High values of LPS and LBP were observed in both groups of patients without significant difference between them. High values of sCD14 were observed in 53.1% of Caucasians and only in 18.8% of African patients (p = 0.0042). A correlation between LPS and sCD14 was observed in Caucasians but not African patients. CONCLUSION: Our observation suggests that factors not related to microbial translocation are responsible for lower sCD14 value in Africans

HIV viraemic patients downregulate CD94/NKG2A inhibitory receptors on NK as well as CD8 T cells in comparison with aviraemic counterparts

Background: The CD94/NKG2 heterodimer is a C-type lectin receptor formed by the association of CD94 and one of the NKG2 molecules (namely NKG2A, -B, -C or –E). The interaction of CD94/NKG2A with non classical HLA-E molecules delivers inhibitory signals. CD94/NKG2A is normally expressed on most NK cells whereas less than 5% of peripheral resting CD8+ T cells are positive. Although several reports have clearly shown an upregulation of CD94 on CD8 T cells in HIV infection, the simultaneous expression of both subunits of the inhibitory receptor on NK and T cells and its relation with viral load is largely unknown. Methods: PBLs from 30 HIV-infected patients (16 viraemic and 14 aviraemic under HAART) and 18 healthy volunteers were analysed by flow cytometry after staining with the following monoclonal antibodies (Percp-conjugated anti-CD8, FITC-conjugated anti-CD3, APC-conjugated anti-CD94, PE-conjugated anti-NKG2A). Results: The proportion of CD8 T cells expressing the CD94/NKG2A inhibitory receptor was not significantly increased in HIV-infected patients (5.68 ± 3.72%) in comparison with non-infected controls (4.90±2.84%). Interestingly, patients with viral load < 50 copies/ml had a higher proportion of CD8 T cells expressing the inhibitory receptor (7.15 ± 3.63%) than patients with HIV viraemia (4.40 ± 3.40%), p= 0.041. The same pattern was observed for NK cells and was even more pronounced. In aviraemic individuals, 61.75 ± 20.39% of NK cells expressed the inhibitory receptor vs 42.88 ± 26.38% in viraemic patients. The proportion of CD94/NKG2A positive cells was correlated between NK and CD8 T cell subsets (p=0.0351) but there was no correlation with absolute or relative CD4 counts. Conclusions: Our results suggest that chronic stimulation with HIV antigens in viraemic patients could lead to decreased rather than increased expression of inhibitory receptors on NK and CD8 T cells. This could contribute to the abnormal activation of the immune system associated with advanced HIV disease

Apexxnar®, 20-valent pneumococcal conjugate vaccine

editorial reviewedStreptococcus pneumoniae infections cause bacteremic and non-bacteremic community-acquired pneumonia and invasive pneumococcal diseases (IPD) such as bacteremia, sepsis and acute meningitis. They are potentially lethal. Although polysaccharide vaccines (PPV23, Pneumovax 23®) have already provided protection in at-risk individuals, they have been imperfect, mainly because the development of anti-polysaccharide antibodies occurs without the help of T cells. The introduction of immunogenic protein conjugate vaccines (ICVs) has overcome this problem and provided better and longer lasting protection. The first available vaccine of this type for adults was Prevenar 13®, targeting 13 polysaccharides of S. pneumoniae (PCV13). A new vaccine, Apexxnar®, targeting 20 polysaccharides (PCV20), the 13 of Prevenar 13®, to which 7 other serotypes considered to be equally responsible for invasive infections have been added, has recently been launched. Clinical studies have demonstrated a good immunogenic response against all 20 serotypes in adult patients who are either vaccine-naive or previously vaccinated with PPV23 and/or PCV13. Furthermore, the tolerance of the PCV20 vaccine was found to be comparable to that of Prevenar 13®. Vaccination with PCV20 involves a single injection. The Belgian Superior Health Council has recently reiterated the importance of vaccinating at-risk individuals against S. pneumoniae (a vaccination that is still under-performed). It now recommends vaccination with PCV20 (Apexxnar®) as the preferred primary vaccination regimen in high-risk adults with co-morbidities or in good health aged between 65 and 85 years.Les infections par le Streptococcus pneumoniae sont responsables de pneumonies communautaires bactériémiantes ou non ainsi que de maladies invasives à pneumocoques (MIP) telles que bactériémies, sepsis et méningites aiguës. Elles sont potentiellement létales. Certes, les vaccins polysaccharidiques (PPV23, Pneumovax 23®) ont déjà permis d’assurer une protection chez les personnes à risque, mais de façon imparfaite essentiellement parce que le développement des anticorps anti-polysaccharides se fait sans l’aide des lymphocytes T. La commercialisation des vaccins conjugués (PCV) à une protéine immunogène a permis de remédier à ce problème et d’assurer une meilleure protection plus durable. Le premier vaccin disponible pour les adultes était le Prevenar 13®, ciblant 13 polysaccharides du S. pneumoniae (PCV13). Un nouveau vaccin vient d’être commercialisé, l’Apexxnar®, ciblant 20 polysaccharides (PCV20), les 13 du Prevenar 13® auquels 7 autres sérotypes considérés comme également responsables d’infections invasives ont été ajoutés. Des études cliniques ont démontré une bonne réponse immunogène contre l’ensemble des 20 sérotypes, chez des personnes adultes naïves de vaccination ou déjà vaccinées antérieurement par le PPV23 et/ou le PCV13. Par ailleurs, la tolérance du vaccin PCV20 s’est révélée comparable à celle du Prevenar 13®. La vaccination avec le PCV20 comporte une injection unique. Le Conseil Supérieur de la Santé Belge vient de rappeler l’importance de vacciner les personnes à risque contre S. pneumoniae (vaccination encore trop peu réalisée). Il recommande désormais la vaccination avec le PCV20 (Apexxnar®) comme schéma préférentiel de primo-vaccination chez les personnes adultes à haut risque, avec comorbidités ou en bonne santé âgées entre 65 et 85 ans

Role of vitamin D in HIV infection

La vitamine D possède des propriétés sur le métabolisme phosphocalcique mais aussi dans diverses pathologies telles que les maladies auto-immunes, les cancers, les maladies cardio-vasculaires, l’excès de poids ou encore certaines infections. Nous nous intéressons ici aux relations frappantes qui existent entre la vitamine D et le VIH. Cette hormone joue assurément un rôle important dans l’infection par le VIH, tant au niveau squelettique qu’au niveau de l’évolution de la maladie elle-même. Nous remarquons en effet qu’un déficit en vitamine D est très souvent associé à l’infection par le VIH. De plus, un taux indétectable de cette hormone chez les patients séropositifs est associé à une infection cliniquement plus avancée et à une mortalité accrue. Ainsi, le déficit en vitamine D doit être considéré comme un cofacteur important de la progression de l’infection par le VIH. En effet, la vitamine D augmente l’activité des macrophages, entre autres via le processus d’autophagie, ce qui permet d’inhiber l’infection par le VIH-1. Nous parlerons ensuite de l’impact de certains traitements antirétroviraux sur l’altération du métabolisme de la vitamine D. Nous évaluerons enfin le bénéfice d’une supplémentation en vitamine D chez ces patients.Peer reviewe

A second update on mapping the human genetic architecture of COVID-19.

peer reviewe

Primary deficiency of interleukin-1 receptor-associated kinase (IRAK-4) presenting as fatal pseudomonas aeruginosa bacteremia in two siblings

Interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency is a primary immunodeficiency of innate immunity. This is the case of a previous healthy toddler and his sibling, who both died of fulminant sepsis due to Pseudomonas aeruginosa. Subsequent genetic analysis demonstrated IRAK-4 deficiency with compound heterozygous splice mutations. Fulminant fatal Pseudomonas aeruginosa sepsis may be the first manifestation of IRAK-4 deficiency

Sleeping

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Downregulation of CD94/NKG2A inhibitory receptors on CD8+ T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated CD8+ T lymphocytes. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In this study, CD94/NKG2A receptor expression on CD8+ T lymphocytes and NK cells was assessed in 46 HIV-1-infected patients (24 viraemic, 22 aviraemic) and 10 healthy volunteers. The percentage of CD8+ T lymphocytes expressing the CD94/NKG2A inhibitory heterodimer was very significantly decreased in HIV-1-infected patients in comparison with non-infected controls. Within the HIV infected patients, the proportion of CD8+ T lymphocytes and NK cells expressing CD94/NKG2A was higher in subjects with undetectable viral loads in comparison with their viraemic counterparts. No significant difference was detected in the proportion of CD8+ T lymphocytes expressing the activatory CD94/NKG2C heterodimer between the HIV-1 infected patients and the healthy donors, nor between the vireamic and avireamic HIV-1 infected patients. In conclusion, chronic stimulation with HIV antigens in viraemic patients leads to a decreased rather than increased CD94/NKG2A expression on CD8+ T lymphocytes and NK cells

Pharmacokinetics of Extended vs Intermittent Intravenous Infusion of Meropenem in Critically Ill Patients Receiving Continuous Veno-Venous Haemofiltration

peer reviewe

Factors associated with the continuum of care of HIV infected patients in Belgium

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