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Our observations establish a causal link between an ezrin-radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-linked moesin-associated immunodeficiency.

GATA2 (n 5 1), and 22q11.2 (n 5 4) mutations and deletions, suggesting improved clinical utility of our comprehensively designed target capture.CVID is the most common PID, representing a heterogeneous group of hypogammaglobulinemias of largely unknown molecular defects. Our system established a genetic diagnosis of 22q11.2 deletion syndrome (22q11.2DS) in a patient with CVID in accordance with a previous study, reporting that a subgroup of patients with adult 22q11.2DS could have hypogammaglobinemia. 9 Moreover, the incidence of this syndrome is relatively high compared with that of other PIDs. Therefore patients with CVID should always be evaluated for the possibility of 22q11.2DS. In this context our customized design to capture this chromosomal lesion is useful.Recent studies revealed that newborn screening for T-cell receptor excision circles can efficiently detect infants with severe combined immunodeficiency and complete DiGeorge syndrome (mainly because of 22q11.2DS). 10 Our comprehensive genetic diagnostic system covering virtually all of the PID genes and 22q11.2DS, would provide an effective genetic confirmation test for infants with positive results on T-cell receptor excision circle screening tests, who require precise and rapid genetic diagnoses for appropriate clinical management.In summary, we developed an NGS-based comprehensive, rapid, and efficient PID diagnostic system that could become a first-line genetic analysis of PID-suspected patients, including infants with positive newborn screening results.We thank the patients and family who made this study possible by providing clinical samples. We also thank Ms Yoshie Miura, Ms Yuko Imanishi, and Ms Hiroe Namizaki for their valuable assistance. We acknowledge the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine, for technical support for NGS. Finally, we thank Enago (www.enago.jp) for the English-language review.

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The cord blood cells, including hematopoietic stem cells, from newborns exposed in utero to a zidovudine-based ARV combination present cytogenetic and transcriptional abnormalities compatible with DNA damage.

EH, et al. Increased peanut-specific IgA levels in saliva correlate with food challenge outcomes after peanut sublingual immunotherapy.

We characterized a new pathway to induce tolerogenic dendritic cells (DCs) following treatment of human monocyte-derived DCs with proteases from the fungus Aspergillus oryzae (ASP). ASP-treated DCs (ASP-DCs) exhibit a CD80−CD83−CD86−Ig-like transcript (ILT)2−ILT3−ILT4+ phenotype, do not secrete cytokines or chemokines, and express tolerogenic markers such as glucocorticoid-induced leucine zipper, NO synthetase-2, retinaldehyde dehydrogenase-1 or retinaldehyde dehydrogenase-2. When cocultured with naive CD4+ T cells, ASP-DCs induce an anergic state that can be reversed by IL-2. Generated T cells mediate a suppressive activity in third-party experiments that is not mediated by soluble factors. A comparison between dexamethasone-treated DCs used as a reference for regulatory T cell-inducing DCs and ASP-DCs reveals two distinct phenotypes. In contrast to dexamethasone, ASP treatment induces glucocorticoid-induced leucine zipper independently of glucocorticoid receptor engagement and leads to NF-κB p65 degradation. Abrogation of protease activities in ASP using specific inhibitors reveals that aspartic acid-containing proteases are key inducers of regulatory genes, whereas serine, cysteine, and metalloproteases contribute to NF-κB p65 degradation. Collectively, those features correspond to a previously unreported anergizing phenotype for human DCs. Such regulatory mechanisms may allow fungi to downregulate host immune responses and provide clues for new approaches to treat proinflammatory disorders.

Background In line with evidence for a role of pathogenic TH2A in seasonal allergies, we previously showed that individuals suffering from food allergy exhibited a decrease in circulating TH2A cells following multi‐food immunotherapy. Herein, we aim to confirm the decline of TH2A cells in individuals undergoing house dust mite immunotherapy (HDM‐AIT) and extend our observation to a new subset of CD38 expressing activated TH2A cells. Methods The frequencies of TH2A and CD38+ TH2A cells were analysed by flow cytometry in blood cells from 182 Japanese HDM‐allergic individuals included in a 1‐year clinical trial assessing the efficacy of HDM tablets. Interrelationship between these cellular responses and humoral mite‐specific IgE and IgG4 levels was further explored. Results A decrease in TH2A cells was observed in both active and placebo groups. Interestingly, CD38+ TH2A cell frequencies significantly decreased only in active groups. In younger individuals (16–30 years), both TH2A and CD38+ TH2A cells were significantly reduced in active groups but not in the placebo group. Significant inverse correlations were observed in the course of HDM‐AIT between changes in TH2A or CD38+ TH2A frequencies and IgG4 antibody levels. Conclusions We confirm the value of monitoring TH2A cell frequencies in allergic individuals and extend this observation to perennial allergy to HDM. We highlight the interest of CD38 to better identify the subset of TH2A cell down‐regulated by AIT. Finally, correlated cellular and humoral responses observed in immunoreactive individuals stress that coordinated pathways occur in the adaptive responses during AIT.