Antoine Froidure

Myeloid dendritic cells are primed in allergic asthma for thymic stromal lymphopoietin-mediated induction of Th2 and Th9 responses.

Type 1 myeloid dendritic cells (mDCs) contribute to inception of allergic asthma (AA) and are regulated by epithelial‐derived cytokines.

Asthma phenotypes and IgE responses.

The discovery of IgE represented a major breakthrough in allergy and asthma research, whereas the clinical interest given to IgE in asthma has been blurred until the arrival of anti-IgE biotherapy. Novel facets of the complex link between IgE and asthma have been highlighted by the effect of this treatment and by basic research. In parallel, asthma phenotyping recently evolved to the concept of endotypes, relying on identified/suspected pathobiological mechanisms to phenotype patients, but has not yet clearly positioned IgE among biomarkers of asthma. In this review, we first summarise recent knowledge about the regulation of IgE production and its main receptor, FcεRI. In addition to allergens acting as classical IgE inducers, viral infections as well as air pollution may trigger the IgE pathway, notably resetting the threshold of IgE sensitivity by regulating FcεRI expression. We then analyse the place of IgE in different asthma endo/phenotypes and discuss the potential interest of IgE among biomarkers in asthma. We summarise regulation of IgE production, and discuss IgE in different asthma endo/phenotypes and among biomarkers http://ow.ly/TLxcW

Impaired ICOSL in human myeloid dendritic cells promotes Th2 responses in patients with allergic rhinitis and asthma

Myeloid dendritic cells (mDCs) and costimulatory molecules such as ICOSL/B7H2 play a pivotal role in murine experimental asthma, while little is known in human allergic disease.

The role of allergen components for the diagnosis of latex-induced occupational asthma.

Recombinant Hevea brasiliensis (rHev b) natural rubber latex (NRL) allergen components have been developed to assess the patients’ allergen sensitization profile and to improve the diagnosis of NRL allergy.

Dendritic cells revisited in human allergic rhinitis and asthma

The role of dendritic cells (DCs) in airway allergy has been studied for 15 years; recent data has highlighted the cross talk with airway epithelial cells and environmental factors (allergens, virus) during the inception and exacerbation of allergic asthma. Although murine models have provided key information, it remains uncertain to what extent these basic mechanisms take place in human allergic disease, notably with regard to different clinical phenotypes. In the present review, we discuss new evidence regarding mechanisms of DC regulation in the mouse which could be important in human asthma. Finally, after discussing the effects of current therapies on DC biology, we focus on pathways that could represent targets for future therapies.

Persistence of asthma following allergen avoidance is associated with proTh2 myeloid dendritic cell activation.

Background The natural history of asthma includes in some patients periods of disease remission, but the underlying mechanisms are unknown. Objectives We explored whether type 1 myeloid dendritic cell (mDC) dysfunction could be involved in the persistence of asthma, studying the controlled setting of occupational asthma after allergen avoidance. Methods We recruited 32 patients with occupational asthma to flour or latex ascertained by specific inhalation challenge and who were no longer exposed to the causal allergen. Leukapheresis was performed in each patient to isolate and characterise blood type 1 mDCs, and their functionality was studied in coculture with allogeneic CD4+ T cells from controls. Results At follow-up, 11/32 patients (34%) were characterised by the absence of symptoms and non-specific bronchial hyper-responsiveness to histamine and were considered to be cured. When compared with cured patients, mDCs from patients with persistent disease increased the production of interleukin (IL) 5 and IL-13 by CD4+ T cells, and upregulated programmed death ligand 2 (PD-L2) upon allergen pulsing. In addition, IL-5 and IL-13 responses could be reversed by exogenous IL-12, as well as by PD-L2 blockade. Conclusions This study indicates that pro-Th2 features of mDCs correlate with disease activity in asthma after cessation of exposure to the causal allergen. The findings also highlight that the Th2 programming by dendritic cells is flexible and partly mediated by PD-L2.

When polymerase chain reaction does not help: cytomegalovirus pneumonitis associated with very low or undetectable viral load in both blood and bronchoalveolar lavage samples after lung transplantation.

Cytomegalovirus (CMV) pneumonitis occurs frequently among solid organ transplant recipients and is classically associated with significant viral replication in both blood and bronchoalveolar lavage (BAL) samples. We present a case of a 64‐year‐old lung transplant recipient who presented with CMV pneumonitis that was diagnosed based on the association of viral inclusion in the BAL sample, rapid response to ganciclovir, and absence of other infectious etiology. Surprisingly, we observed very low or undetectable viral load both in blood and BAL samples. Diagnosis of CMV pneumonitis should rely on the association of clinical, pathological, radiological, and microbiological signs, while quantitative nucleic acid amplification testing should be interpreted with caution.

Defects in Plasmacytoid Dendritic Cell Expression of Inducible Costimulator Ligand and IFN-α Are Associated in Asthma with Disease Persistence.

Plasmacytoid dendritic cells (pDCs) represent a subset of DCs specialized in antiviral defense. Originating from a different lineage than myeloid DCs and displaying a plasma cell–like morphology, they are able to secrete large amounts of type 1 IFN when activated by viruses through toll-like receptor 7 (TLR7) and TLR9 (1). In addition to their antiviral function, pDCs play a role in peripheral tolerance to allergens; in a seminal study, de Heer and colleagues showed that allergen-pulsed pDCs were able to restore tolerance in experimental ovalbumin-induced asthma (2). In addition, it was shown that pDCs from patients with asthma display impaired IFN-a secretion on TLR9 ligation by A-CpG (3). pDC-mediated tolerance is notably related to their expression of the ligand to inducible costimulatory molecule (ICOS-L), as the ICOS/ICOS-L costimulatory pathway has been linked to the priming of IL-10– producing regulatory T cells (4) and to tumor-induced tolerance (5). Mechanisms underlying the persistence of allergic asthma remain poorly understood. This could be related to a multitude of factors that may contribute to disease persistence, among which are persistent allergen exposure and host-related factors. IgE-mediated occupational asthma (OA) offers a unique opportunity to address this question, as one third of patients completely recover (from both symptoms and nonspecific bronchial hyper-responsiveness) after complete cessation of exposure to the causal allergen (6). Given their tolerogenic role, we sought to explore pDCs for their expression of ICOS-L and IFN-a production in 29 patients with OA diagnosis to flour (n = 14) or latex (n = 15), according to a specific inhalation challenge (performed between 2001 and 2011). All patients had been removed from their workplace and were no longer exposed to the causal allergen. Study subjects were defined

Conversion from calcineurin inhibitors to sirolimus in kidney transplant recipients: a retrospective cohort study.

BACKGROUND Replacing a calcineurin inhibitor (CNI) with sirolimus (SRL) may preserve kidney graft function. However, at the present time, only short follow-up after conversion is available. The aim of this study was to assess whether conversion from a CNI-based to an SRL-based maintenance regimen was safe and effective. MATERIALS AND METHODS We performed a retrospective cohort study among kidney graft patients whose CNI was withdrawn to be replaced by SRL. Two-tailed paired t tests were used to compare glomerular filtration rates (GFRs) and proteinuria levels before and up to 2 years after conversion. We used linear regression to determine the factors associated with changes in renal function after conversion. RESULTS The 193 study subjects had a mean GFR at conversion of 41 +/- 16 mL/min/1.73 m(2) a median proteinuria level of 0 g/L (interquartile range = 0-0.15). After conversion, the GFR was stable: at 1 year, the change was -0.34 mL/min/1.73 m(2) (95% confidence interval [CI] = -2.71, 2.03) and at 2 years, -0.96 mL/min/1.73 m(2) (95% CI = 4.26, 2.34). There was a small but significant increase in dipstick proteinuria at 1 year of +0.5 g/L, (95% CI = 0.20, 0.75). On multivariate analysis, proteinuria > or = 1 g/L at the time of conversion was the only predictor of deteriorating GFR at 1 year (beta: -7.91 mL/min/1.73 m(2); 95% CI = -14.10, -1.70). SRL had to be discontinued in 31% of patients. CONCLUSION Conversion from CNI to SRL resulted in stable graft function at 2 years and in a slight increase in proteinuria. Despite the relatively high reconversion rate, this strategy offers a reasonable alternative to CNIs for most patients.

DRESS syndrome in a patient with cystic fibrosis: A case report

Drug reaction with eosinophilia and systemic symptom (DRESS) syndrome is a rare and severe side‐effect, mainly described after intake of anticonvulsants, allopurinol, or antibiotics. It usually begins within 2 months after drug introduction. Symptoms include cutaneous rash, hematologic abnormalities, and internal organ involvement and the diagnosis might be challenging. This case report illustrates for the first time this life‐threatening complication in a patient with cystic fibrosis (CF). In this case, withdrawal of the offending drug was sufficient for full recovery. Clinicians involved in CF care should be aware of DRESS syndrome, as they commonly prescribe several potentially culprit drugs. Pediatr Pulmonol. 2017;52:E18–E21.