Rituximab et maladie du greffon contre l'hôte chronique

La maladie du greffon contre l’hôte (« greffe-versus-hôte » – GVH) chronique (GVHc) est une complication fréquente des allogreffes de cellules souches hématopoïétiques (CSH). A l’heure actuelle, à l’exception des corticostéroïdes, peu de traitements se sont avérés réellement efficaces pour la prise en charge de la GVHc. Des données récentes suggèrent un rôle important des lymphocytes B (LB) dans la physiopathologie de la GVHc. Elles constituent le rationnel scientifique à une série d’études évaluant l’efficacité du rituximab, un anticorps monoclonal dirigé contre l’antigène CD20 exprimé à la surface des LB, dans la prévention ou le traitement de la GVHc.Peer reviewe

The Ballpark podcast Episode 2: This is not a hot take

In this week’s episode of The Ballpark, hosts Denise Baron, Sophie Donszelmann, and Chris Gilson dive into the current state of American politics, but instead of giving you a “hot take,” present you with a historical perspective from 1920 and a political theory on polarisation

Introducing The Ballpark podcast and Episode 1: The Strongest Economy for Who?

Today the LSE US Centre launches its new podcast, The Ballpark, a regular online audio show on US politics, policy, and research. In each episode, hosts Denise Baron, Sophie Donszelmann, and Chris Gilson take a closer look at American politics, economics, policy and news. We’ll feature and dissect the research of academics from the LSE and around the world. This is your chance to go beyond the headlines and get the facts, figures, quotes, and context to form a more informed view on the United States

Allogreffe de cellules souches hématopoïétiques après conditionnements réduits ("minigreffes") comme traitement de certaines pathologies hématologiques malignes

peer reviewedL’allogreffe de cellules souches hématopoïétiques est un trai¬tement efficace, proposé pour la prise en charge d’un grand nombre de pathologies hématologiques malignes. Le concept des allogreffes de cellules souches hématopoïétiques après un conditionnement réduit (appelées «minigreffes») repose sur deux principes essentiels: une toxicité moindre du condi¬tionnement limitant la morbidité et la mortalité reliées à la greffe et l’immunothérapie antitumorale (effet «greffe-ver¬sus-tumeur») comme mécanisme principal de l’éradication des cellules malignes. Les minigreffes ont démontré des résul¬tats encourageants dans de nombreuses pathologies héma¬tologiques malignes. Elles permettent aux patients inéligibles pour une greffe de cellules souches conventionnelle avec un conditionnement myéloablatif de bénéficier de l’effet (poten¬tiellement curatif) de la greffe contre la tumeur. Au travers de cet article, nous proposons une revue de la littérature concernant les fondements conceptuels des minigreffes de cellules souches hématopoïétiques, les particularités de ce type de greffes, les effets secondaires possibles, les résultats obtenus dans plusieurs pathologies hématologiques malignes ainsi que les indications actuellement reconnues

The three lipocalins of egg-white: only Ex-FABP inhibits siderophore-dependent iron sequestration by Salmonella Enteritidis

Salmonella Enteritidis is the most prevalent food-borne pathogen associated with egg-related outbreaks in the European Union. During egg colonization, S. Enteritidis must resist the powerful anti-bacterial activities of egg white (EW) and overcome ovotransferrin-imposed iron-restriction (the most important anti-bacterial mechanism of EW). Many pathogens respond to iron restriction by secreting iron-chelating chemicals called siderophores but EW contains a siderophore-sequestering “lipocalin” protein (Ex-FABP) that is predicted to limit the usefulness of siderophores in EW. S. Enteritidis produces two siderophores: enterobactin, which is strongly bound by Ex-FABP; and the di-glucosylated enterobactin-derivative, salmochelin (a so-called “stealth” siderophore), which is not recognized by Ex-FABP. Thus, production of salmochelin may allow S. Enteritidis to escape Ex-FABP-mediated growth inhibition under iron restriction although it is unclear whether its EW concentration is sufficient to inhibit pathogens. Further, two other lipocalins (Cal-γ and α-1-ovoglycoprotein) are found in EW but their siderophore sequestration potential remains unexplored. In addition, the effect of EW lipocalins on the major EW pathogen, S. Enteritidis, has yet to be reported. We overexpressed and purified the three lipocalins of EW and investigated their ability to interact with the siderophores of S. Enteritidis, as well as their EW concentrations. The results show that Ex-FABP is present in EW at concentrations (5.1 μM) sufficient to inhibit growth of a salmochelin-deficient S. Enteritidis mutant under iron restriction but has little impact on the salmochelin-producing wildtype. Neither Cal-γ nor α-1-ovoglycoprotein bind salmochelin or enterobactin, nor do they inhibit iron-restricted growth of S. Enteritidis. However, both are present in EW at significant concentrations (5.6 and 233 μM, respectively) indicating that α-1-ovoglycoprotein is the 4th most abundant protein in EW, with Cal-γ and Ex-FABP at 11th and 12th most abundant. Further, we confirm the preference (16-fold) of Ex-FABP for the ferrated form (Kd of 5.3 nM) of enterobactin over the iron-free form (Kd of 86.2 nM), and its lack of affinity for salmochelin. In conclusion, our findings show that salmochelin production by S. Enteritidis enables this key egg-associated pathogen to overcome the enterobactin-sequestration activity of Ex-FABP when this lipocalin is provided at levels found in EW

Bacterial diversity on stainless steel surfaces of egg processing companies and potential of selected isolates to spoil liquid whole egg products

AimsTo assess the bacterial diversity in the French egg processing industry and to explore the adhesion and spoilage potential of selected bacteria.Methods and ResultsSterile stainless steel chips were suspended for 2 months inside the pipelines of seven egg processing companies, before and after the pasteurizer, at warm and cold seasons. After exposure, the bacterial diversity was assessed by 16S rDNA sequencing. The 231 collected isolates were mainly facultative anaerobic Gram positive bacteria, such as Streptococcus, Staphylococcus, Bacillus and Kocuria. Sixty‐five representative isolates were further characterized in vitro regarding the potential for adhesion and egg product spoilage. A high diversity was observed from one genus to another. Kocuria and Rothia isolates showed significantly higher adhesion than the isolates of the other genera. Only the isolates belonging to the genera Bacillus and Lysinibacillus, associated with high enzymatic activities on a solid egg‐based medium, were able to induce spoilage of liquid whole egg.ConclusionsBacteria collected on stainless steel surfaces placed in egg processing industries could be associated to liquid egg product spoilage.Significance and Impact of the StudyThis study provides new insights on the bacterial contamination in egg processing companies and represents a first step for the effective control of undesirable bacteria in liquid egg products

Rapamycin prevents experimental sclerodermatous chronic graft-versus-host disease in mice

Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that mortality is relatively low, making difficult to study the impact of potentially therapeutic compounds. Aims: To develop a more severe model of cGVHD and to assess the impact of Rapamycin administration in that model. Results: Lethally irradiated Balb/C mice were injected with 10x106 bone marrow cells and 70x106 splenocytes from B10.D2 donor mice. Twenty-one days later, all mice developed cGvHD. For the severe model, donor B10.D2 mice were injected with 0.5x106 splenocytes from Balb/C twenty-one days before transplantation. All mice from the severe model (n=8) died a median of 32 days while 3 of 7 mice in the classical model survived beyond day 52. Mean survival was decreased in the severe model compared to the classical model (32 days versus 37 days; p=0.0185). Recipient mice in the severe group experienced higher weight loss, hair loss and skin fi brosis. Numbers of T lymphocytes (231.9 ± 151.4 versus 951 ± 532.8; p=0.0032) and CD4+ T cells (63.25 ± 41.93 versus 135.0 ± 14.39; p=0.0018) per microliter of blood at day 21 were lower in the severe group than in the classical model. Moreover, number of regulatory T cells (Tregs) was decreased in the severe model (1.250 ± 0.8864 versus 8.000 ± 6.753; p=0.0151). We then investigated whether rapamycin administration could prevent GVHD in the severe model. All (n=8) mice treated with PBS (placebo) died a median of 32 days after transplantation, while 6 of 8 mice given 1 mg/kg/day i.p. rapamycin survived beyond day 52 (p=0.0012). Number of Tregs/μl was higher at day 21 in rapamycin-treated mice than in mice given PBS (2.000±1.195 versus 1.250±0.8864; p=0.0796). Moreover, number of naïve CD4+T (10.00±4.192 versus 30.25±5.185; p= 0.0089) and effector memory T cells (EMT) (30.67±3.180 versus 67.33±7.881; p= 0.0125) were higher in rapamycin mice. Finally, proliferation of EMT (assessed by fl ow cytometry using Ki-67) was higher in PBS than in rapamycin mice (45.28%±4.084 versus 31.90%± 2.003; p=0.0474). Conclusion: We have developed a mice model of severe cGVHD. Interestingly, rapamycin prevented death from cGVHD in that model, perhaps through in vivo expansion of Treg

The Ballpark podcast episode 3: power, person, people: US foreign policy

In this week’s episode of The Ballpark, hosts Denise Baron, Sophie Donszelmann, and Chris Gilson take a look at contemporary theories around American power and the factors that influence US foreign policy