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The aim of our study was to determine whether granzyme B-expressing regulatory B cells (GZMB+ B cells) are enriched in the blood of transplant patients with renal graft tolerance. To achieve this goal, we analysed two single-cell RNA sequencing (scRNAseq) datasets: (1) peripheral blood mononuclear cells (PBMCs), including GZMB+ B cells from renal transplant patients, i.e., patients with stable graft function on conventional immunosuppressive treatment (STA, n = 3), drug-free tolerant patients (TOL, n = 3), and patients with antibody-mediated rejection (ABMR, n = 3), and (2) ex-vivo-induced GZMB+ B cells from these groups. In the patient PBMCs, we first showed that natural GZMB+ B cells were enriched in genes specific to Natural Killer (NK) cells (such as NKG7 and KLRD1) and regulatory B cells (such as GZMB, IL10, and CCL4). We performed a pseudotemporal trajectory analysis of natural GZMB+ B cells and showed that they were highly differentiated B cells with a trajectory that is very different from that of conventional memory B cells and linked to the transcription factor KLF13. By specifically analysing GZMB+ natural B cells in TOLs, we found that these cells had a very specific transcriptomic profile associated with a reduction in the expression of HLA molecules, apoptosis, and the inflammatory response (in general) in the blood and that this signature was conserved after ex vivo induction, with the induction of genes associated with migration processes, such as CCR7, CCL3, or CCL4. An analysis of receptor/ligand interactions between these GZMB+/− natural B cells and all of the immune cells present in PBMCs also demonstrated that GZMB+ B cells were the B cells that carried the most ligands and had the most interactions with other immune cells, particularly in tolerant patients. Finally, we showed that these GZMB+ B cells were able to infiltrate the graft under inflammatory conditions, thus suggesting that they can act in locations where immune events occur. [ABSTRACT FROM AUTHOR]

The article offers information on the diagnosis of hypersensitivity reaction (HSR) to iodinated contrast media (ICM) is challenging when based on clinical history and skin tests. It mentions the objective of this study was to determine the negative predictive value (NPV) for skin tests as compared with the intravenous provocation tests (IPT) 50 mL; and also mentions the IPT was reduced to 10 mL with glomerular filtration rate (GFR).

Background. Recurrent wheezing in infants is a recognized risk factor for the development of childhood asthma. We sought to develop an easy-to-use persistent asthma predictive score (PAPS) in a population of young recurrent wheezers. Methods. We retrospectively studied clinical and biological data of infants under 2 years of age presenting recurrent wheezing and evaluated current asthma at 6 years of age using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Multivariate analysis was performed to select predictive variables to generate a PAPS. The score was then tested on another cohort for independent validation. Results. Two hundred infants were included in the cohort used to create the PAPS, and 227 in the validation cohort. In the first population, 47% of the children had developed asthma at 6 years of age, including 33% with mild to severe persistent asthma. Three parameters independently predicted persistent asthma: family history of asthma, personal atopic dermatitis, and multiple allergen sensitizations. Based on these variables, the PAPS showed 42% sensitivity, 90% specificity, 67% positive predictive value, and 76% negative predictive value for the prediction of persistent asthma. It was able to discriminate future persistent asthmatic from nonfuture persistent asthmatic children, with an accuracy of 74% in the initial population and 67% in the validation population. Conclusions. The PAPS, based on three easy-to-obtain variables, could help the physician in clinical practice to identify infants at high risk for persistent childhood asthma, and thus better evaluate the need for secondary preventive measures. [ABSTRACT FROM AUTHOR]