Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

Background: Activated phosphoinositide-3-kinase d syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. Objectives: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain of-function (GOF) disease; and identify predictors of severity in APDS. Methods: Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs. Results: The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. Conclusions: APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients. (J Allergy Clin Immunol 2023;152:984-96.

Profils sociodémographiques et psychiatriques des victimes d'immolation par le feu

TOURS-BU Médecine (372612103) / SudocSudocFranceF

Le capital d’autochtonie, un concept pour (re)penser les rapports sociaux ?

International audience«ÊTRE du coin », « venir d’ici », « être du cru », « être un enfant du pays », autant d’expressions qui traduisent le poids de l’appartenance locale pour les individus et les collectifs. La valorisation du « local » est aujourd’hui un argument qui tend à devenir de plus en plus récurrent et prégnant dans les discours, qu’ils soient politiques, commerciaux ou ordinaires. Face à la production de ces discours, de jeunes chercheurs en sciences sociales ont souhaité proposer un éclairage scientifique à partir d’enquêtes empiriques variées : du rural à l’urbain, des militants pour la décroissance aux bûcherons en passant par les agriculteurs biologiques ou encore les danseurs de hip-hop. La multiplicité des terrains sur lesquels reposent les sept analyses proposées témoigne d’ailleurs de la diversité des lieux et des contextes où l’usage de la catégorie « local » est susceptible d’êtremobilisé. Unis par une volonté commune de comprendre les ressorts de ce recours au local, l’ensemble des contributeurs de cet ouvrage cherche à interroger le concept de capital d’autochtonie – défini comme « l’ensemble des ressources que procure l’appartenance à des réseaux de relations localisées » – afin de saisir le sens que peuvent revêtir aujourd’hui les arguments de celles et ceux qui font de leur ancrage local une ressource sociale à valoriser. Ils invitent en ce sens à repenser la construction et la transformation des rapports sociaux dans le temps à partir des réseaux sociaux locaux. Cet ouvrage, à travers le regard interdisciplinaire qu’il porte – alliant sociologie, sciences politiques et géographie sociale –, se veut un prolongement aux études et réflexions menées sur l’usage aujourd’hui renouvelé du concept de capital d’autochtonie et plus largement, une contribution à la compréhension des logiques sociales attenantes aux discours et postures de valorisation du local

Azole Resistance in Aspergillus fumigatus: A Five-Year Follow Up Experience in a Tertiary Hospital With a Special Focus on Cystic Fibrosis

National audienceAzole-resistant (AR) has emerged worldwide during the last decades. Drug pressure after long term treatments of chronically infected patients and the propagation of environmental clones selected under the pressure of imidazoles fungicides used in agriculture and farming both account for this emergence. The objectives of this study were to determine the rate of azole resistance in during a 5-year period, taking into account (i) differences between underlying diseases of the patients treated, (ii) cross-resistance between azoles, and (iii) focusing on the 5-year evolution of our center's cystic fibrosis cohort. Overall, the rates of voriconazole (VRC)-resistant and itraconazole (ITC)-resistant isolates were 4.1% (38/927) and 14.5% (95/656), respectively, corresponding to 21/426 (4.9%) and 44/308 (14.3%) patients, respectively. Regarding cross-resistance, among VRC-R isolates tested for ITC, nearly all were R (20/21;95%), compared to only 27% (20/74) of VRC-R among ITC-R isolates. The level of azole resistance remained somewhat stable over years but greatly varied according to the azole drug, patient origin, and clinical setting. Whereas azole resistance during invasive aspergillosis was very scarce, patients with cystic fibrosis were infected with multiple strains and presented the highest rate of resistance: 5% (27/539) isolates were VRC-R and 17.9% (78/436) were ITC-R. These results underline that the interpretation of the azole resistance level in in a routine setting may consider the huge variability depending on the azole drug, the clinical setting, the patient background and the type of infection

Relevance of using both aerobic and anaerobic enrichment vials for optimizing rapid diagnosis of osteoarticular infections

International audienceThe performance of a pair of blood culture vials (BACTEC® Plus Aerobic/F, and Anaerobic Lytic/F) were analyzed in 496 osteoarticular specimens (246 synovial fluids and 250 crushed bone samples), obtained in patients during routine diagnostic procedure at the Teaching Hospital of Rennes (France). The positive detection times were recorded for a 14 day-incubation period, and compared between both vials and with agar cultures. For samples from infected patients, the positive detection time was significantly shortened when vials were used compared to agar plates (p < 0.001). Median positive detection time was later with the Anaerobic Lytic/F vials (15.0 h) compared to the Plus Aerobic/F (13.0 h). Positivity rate was similar for Anaerobic Lytic/F vials (80.4%) and Plus Aerobic/F vials (83.2%) (p = 0.25). Some microorganisms were only identified from aerobic vials (15.5%) or from anaerobic vials (12.7%). The use of both atmosphere conditions for optimal positive detection time is therefore critical

MCAM/CD146 Defines and Regulates the Function of a Population of Human Effector Memory Th17 Lymphocytes Subset Involved in Neuroinflammation

Interaction between adhesion molecules on blood-brain barrier endothelial cells (BBB-ECs) and their cognate ligand on lymphocytes promotes transmigration to the CNS. Our data demonstrate that Melanoma Cell Adhesion Molecule (MCAM/CD146) is expressed by a subset of effector memory CD4+ T lymphocytes, co-expressing CD95, CD147, CD11a, CD49d and CCR6. In vitro polyclonal activation induced MCAM expression on as much as 60% of CD4+CD45RO+ lymphocytes. MCAM+ lymphocytes also expressed more ROR\u3b3 and IL-17 than MCAMneg cells, but comparable levels of IFN\u3b3, IL-2 and GM-CSF both ex vivo and after polyclonal activation. The proportion of MCAM+ lymphocytes was found to be higher in the blood of MS patients than in healthy controls, and was enriched in the CSF of MS patients. When compared to MCAM+ cells obtained from healthy control donors, MCAM+ lymphocytes from MS patients consistently produced more IL-17, in percentage and intensity. During IL-23-driven in vitro polarization of lymphocytes, functional inactivation of MCAM significantly reduced both lymphocyte proliferation and IL-17 production. We further found that MCAM is expressed on the surface of human BBB-ECs in vitro and in situ in MS lesions and that MCAM blockers decreased the recruitment of MCAM+ lymphocytes across BBB-ECs. Our data indicate that MCAM is expressed by both BBB-ECs and a subset of IL-17-expressing effector memory CD4 lymphocytes and that MCAM engagement promotes both IL-17 expression in lymphocytes, as well as the recruitment of these cells across BBB-ECs.Peer reviewed: YesNRC publication: Ye