IL-7 Promotes CD95-Induced Apoptosis in B Cells via the IFN-γ/STAT1 Pathway

Interleukin-7 (IL-7) concentrations are increased in the blood of CD4+ T cell depleted individuals, including HIV-1 infected patients. High IL-7 levels might stimulate T cell activation and, as we have shown earlier, IL-7 can prime resting T cell to CD95 induced apoptosis as well. HIV-1 infection leads to B cell abnormalities including increased apoptosis via the CD95 (Fas) death receptor pathway and loss of memory B cells. Peripheral B cells are not sensitive for IL-7, due to the lack of IL-7Ra expression on their surface; however, here we demonstrate that high IL-7 concentration can prime resting B cells to CD95-mediated apoptosis via an indirect mechanism. T cells cultured with IL-7 induced high CD95 expression on resting B cells together with an increased sensitivity to CD95 mediated apoptosis. As the mediator molecule responsible for B cell priming to CD95 mediated apoptosis we identified the cytokine IFN-γ that T cells secreted in high amounts in response to IL-7. These results suggest that the lymphopenia induced cytokine IL-7 can contribute to the increased B cell apoptosis observed in HIV-1 infected individuals

CD27− B-Cells Produce Class Switched and Somatically Hyper-Mutated Antibodies during Chronic HIV-1 Infection

Class switch recombination and somatic hypermutation occur in mature B-cells in response to antigen stimulation. These processes are crucial for the generation of functional antibodies. During HIV-1 infection, loss of memory B-cells, together with an altered differentiation of naïve B-cells result in production of low quality antibodies, which may be due to impaired immunoglobulin affinity maturation. In the current study, we evaluated the effect of HIV-1 infection on class switch recombination and somatic hypermutation by studying the expression of activation-induced cytidine deaminase (AID) in peripheral B-cells from a cohort of chronically HIV-1 infected patients as compared to a group of healthy controls. In parallel, we also characterized the phenotype of B-cells and their ability to produce immunoglobulins in vitro. Cells from HIV-1 infected patients showed higher baseline levels of AID expression and increased IgA production measured ex-vivo and upon CD40 and TLR9 stimulation in vitro. Moreover, the percentage of CD27−IgA+ and CD27−IgG+ B-cells in blood was significantly increased in HIV-1 infected patients as compared to controls. Interestingly, our results showed a significantly increased number of somatic hypermutations in the VH genes in CD27− cells from patients. Taken together, these results show that during HIV-1 infection, CD27− B-cells can also produce class switched and somatically hypermutated antibodies. Our data add important information for the understanding of the mechanisms underlying the loss of specific antibody production observed during HIV-1 infection

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21\u201328 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age>65 years, antiviral treatment and for severe disease, lactate dehydrogenase >300 mg/dL

Lack of SARS-CoV-2 RNA environmental contamination in a tertiary referral hospital for infectious diseases in Northern Italy

none140noNAnoneColaneri M.; Seminari E.; Piralla A.; Zuccaro V.; Di Filippo A.; Baldanti F.; Bruno R.; Mondelli M.U.; Brunetti E.; Di Matteo A.; Maiocchi L.; Pagnucco L.; Mariani B.; Ludovisi S.; Lissandrin R.; Parisi A.; Sacchi P.; Patruno S.F.A.; Michelone G.; Gulminetti R.; Zanaboni D.; Novati S.; Maserati R.; Orsolini P.; Vecchia M.; Sciarra M.; Asperges E.; Sambo M.; Biscarini S.; Lupi M.; Roda S.; Chiara Pieri T.; Gallazzi I.; Sachs M.; Valsecchi P.; Perlini S.; Alfano C.; Bonzano M.; Briganti F.; Crescenzi G.; Giulia Falchi A.; Guarnone R.; Guglielmana B.; Maggi E.; Martino I.; Pettenazza P.; Pioli di Marco S.; Quaglia F.; Sabena A.; Salinaro F.; Speciale F.; Zunino I.; De Lorenzo M.; Secco G.; Dimitry L.; Cappa G.; Maisak I.; Chiodi B.; Sciarrini M.; Barcella B.; Resta F.; Moroni L.; Vezzoni G.; Scattaglia L.; Boscolo E.; Zattera C.; Michele Fidel T.; Vincenzo C.; Vignaroli D.; Bazzini M.; Iotti G.; Mojoli F.; Belliato M.; Perotti L.; Mongodi S.; Tavazzi G.; Marseglia G.; Licari A.; Brambilla I.; Daniela B.; Antonella B.; Patrizia C.; Giulia C.; Giuditta C.; Marta C.; Rossana D.; Milena F.; Bianca M.; Roberta M.; Enza M.; Stefania P.; Maurizio P.; Elena P.; Antonio P.; Francesca R.; Antonella S.; Maurizio Z.; Guy A.; Laura B.; Ermanna C.; Giuliana C.; Luca D.; Gabriella F.; Gabriella G.; Alessia G.; Viviana L.; Claudia L.; Valentina M.; Simona P.; Marta P.; Alice B.; Giacomo C.; Irene C.; Alfonso C.; Di Martino R.; Di Napoli A.; Alessandro F.; Guglielmo F.; Loretta F.; Federica G.; Alessandra M.; Federica N.; Giacomo R.; Beatrice R.; Maria S.I.; Monica T.; Nepita Edoardo V.; Calvi M.; Tizzoni M.; Nicora C.; Triarico A.; Petronella V.; Marena C.; Muzzi A.; Lago P.; Comandatore F.; Bissignandi G.; Gaiarsa S.; Rettani M.; Bandi C.Colaneri, M.; Seminari, E.; Piralla, A.; Zuccaro, V.; Di Filippo, A.; Baldanti, F.; Bruno, R.; Mondelli, M. U.; Brunetti, E.; Di Matteo, A.; Maiocchi, L.; Pagnucco, L.; Mariani, B.; Ludovisi, S.; Lissandrin, R.; Parisi, A.; Sacchi, P.; Patruno, S. F. A.; Michelone, G.; Gulminetti, R.; Zanaboni, D.; Novati, S.; Maserati, R.; Orsolini, P.; Vecchia, M.; Sciarra, M.; Asperges, E.; Sambo, M.; Biscarini, S.; Lupi, M.; Roda, S.; Chiara Pieri, T.; Gallazzi, I.; Sachs, M.; Valsecchi, P.; Perlini, S.; Alfano, C.; Bonzano, M.; Briganti, F.; Crescenzi, G.; Giulia Falchi, A.; Guarnone, R.; Guglielmana, B.; Maggi, E.; Martino, I.; Pettenazza, P.; Pioli di Marco, S.; Quaglia, F.; Sabena, A.; Salinaro, F.; Speciale, F.; Zunino, I.; De Lorenzo, M.; Secco, G.; Dimitry, L.; Cappa, G.; Maisak, I.; Chiodi, B.; Sciarrini, M.; Barcella, B.; Resta, F.; Moroni, L.; Vezzoni, G.; Scattaglia, L.; Boscolo, E.; Zattera, C.; Michele Fidel, T.; Vincenzo, C.; Vignaroli, D.; Bazzini, M.; Iotti, G.; Mojoli, F.; Belliato, M.; Perotti, L.; Mongodi, S.; Tavazzi, G.; Marseglia, G.; Licari, A.; Brambilla, I.; Daniela, B.; Antonella, B.; Patrizia, C.; Giulia, C.; Giuditta, C.; Marta, C.; D'Alterio, Rossana; Milena, F.; Bianca, M.; Roberta, M.; Enza, M.; Stefania, P.; Maurizio, P.; Elena, P.; Antonio, P.; Francesca, R.; Antonella, S.; Maurizio, Z.; Guy, A.; Laura, B.; Ermanna, C.; Giuliana, C.; Luca, D.; Gabriella, F.; Gabriella, G.; Alessia, G.; Viviana, L.; Meisina, Claudia; Valentina, M.; Simona, P.; Marta, P.; Alice, B.; Giacomo, C.; Irene, C.; Alfonso, C.; Di Martino, R.; Di Napoli, A.; Alessandro, F.; Guglielmo, F.; Loretta, F.; Federica, G.; Albertini, Alessandra; Federica, N.; Giacomo, R.; Beatrice, R.; Maria, S. I.; Monica, T.; Nepita Edoardo, V.; Calvi, M.; Tizzoni, M.; Nicora, C.; Triarico, A.; Petronella, V.; Marena, C.; Muzzi, A.; Lago, P.; Comandatore, F.; Bissignandi, G.; Gaiarsa, S.; Rettani, M.; Bandi, C

Prognostic value of antigen expression in multiple myeloma: a PETHEMA/GEM study on 1,265 patients enrolled in four consecutive clinical trials

Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols. Overall, CD19pos, CD27neg, CD38lo, CD45pos, CD81pos, CD117neg and CD138lo expression predicted inferior outcomes. Through principal component analysis, we found that simultaneous CD38lowCD81posCD117neg expression emerged as the most powerful combination with independent prognostic value for progression-free survival (HR:1.69; P=0.002). This unique phenotypic profile retained prognostic value among MRD-positive patients. We then used next-generation flow to determine antigen stability throughout the course of the disease, and found that the expression of antigens required to monitor MRD is mostly stable from diagnosis to MRD stages, except for CD81 whose expression progressively increased from baseline to chemoresistant tumor cells (14 vs 28%). Altogether, we showed that the phenotypic profile of tumor cells provides additional prognostic information, and could be used to further predict risk of relapse among MRD-positive patients

SPOT5 imagery for soil salinity assessment in Iraq

Soil salinization is a form of topsoil degradation due to the formation of soluble salts at deleterious levels. This phenomenon can seriously compromise vegetation health and agricultural productivity, and represents a worldwide environmental problem. Remote sensing is a very useful tool for soil salinization monitoring and assessment. In this work we show some results of a study aimed to define a methodology for soil salinity assessment in Iraq based on SPOT 5 imagery. This methodology allows the identification of salinized soils primarily on bare soils. Subsequently some soil salinity assessment can be done on vegetated soils. On bare soil the identification of salt is based on spectral analysis, using the Minimum Noise Fraction transformation and several indexes found in literature. In case of densely vegetated soils the methodology for the discrimination of salinized soils has been integrated with the results obtained from the classification of vegetation coverage. © (2012) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

Prognostic value of antigen expression in multiple myeloma: a PETHEMA/GEM study on 1265 patients enrolled in four consecutive clinical trials

Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols. Overall, CD19 pos, CD27 neg, CD38 lo, CD45 pos, CD81 pos, CD117 neg and CD138 lo expression predicted inferior outcomes. Through principal component analysis, we found that simultaneous CD38 low CD81 pos CD117 neg expression emerged as the most powerful combination with independent prognostic value for progression-free survival (HR:1.69; P=0.002). This unique phenotypic profile retained prognostic value among MRD-positive patients. We then used next-generation flow to determine antigen stability throughout the course of the disease, and found that the expression of antigens required to monitor MRD is mostly stable from diagnosis to MRD stages, except for CD81 whose expression progressively increased from baseline to chemoresistant tumor cells (14 vs 28%). Altogether, we showed that the phenotypic profile of tumor cells provides additional prognostic information, and could be used to further predict risk of relapse among MRD-positive patients.On behalf of the GEM (Grupo Español de Mieloma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group. This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología - del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369; CB16/12/00400; CB16/12/00233; CB16/12/00284), formerly named as Cooperative Research Thematic Network (Grants No. RD12/0036/0058, RD12/0036/0048, RD12/0036/0046, and RD12/0036/0061) of the Red de Cancer (Cancer Network of Excellence); Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria; funded in part by the European Regional Development Fund (FIS No. 98/1239, 00/10160, 01/0089, 02/0089, 02/0905, G03/136, PI051284, PI06033906/1354, PS09/01897/01370, PI12/01761, PI12/ 02311, PI13/01469, PI14/01867, G03/136); Sara Borrell (No. CD13/00340); Asociación Española Contra el Cáncer (GCB120981SAN). This study was also supported internationally by the Black Swan Research Initiative of the International Myeloma Foundation, the Qatar National Research Fund (QNRF) Award No. 7-916-3-237, the AACR-Millennium Fellowship in Multiple Myeloma Research (15-40-38-PAIV), the Leukemia Research Foundation, and the European Research Council (ERC) 2015 Starting Grant (MYELOMANEXT).Peer Reviewe

Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy

CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21\u201328 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age>65 years, antiviral treatment and for severe disease, lactate dehydrogenase >300 mg/dL