We identify that MS4A6A is expressed in human mast cells and has high sequence homology to FcεRIβ. We show that MS4A6A contains a putative hemi-ITAM that may function similarly to the FcεRIβ ITAM. We demonstrate that MS4A6A and FcεRIβ perform at least partially redundant roles in FcεRI complex trafficking and function.Abbreviations: Ag, antigen; Ca²⁺, calcium ion; FcεRI, high-affinity IgE receptor; ITAM, immunoreceptor tyrosine-based activation motif; Lyn, Src family tyrosine kinase; MS4A6A, membrane-spanning 4-domains A6A; PLC, phospholipase C; Syk, spleen associated tyrosine kinase

Epidemiological study discovers novel associations between high intake of dietary sucrose and starch with current asthma in males and females, respectively. High-carbohydrate feeding in mice aggravates allergic outcomes: serum IgE, lung inflammatory cell infiltration, T_H2- or T_H2-T_H17 profiles and mucus hypersecretion. Dietary carbohydrate-driven enhanced pulmonary oxidative stress and decreased systemic anti-oxidative capacity are involved in this context.Abbreviations: APE, aqueous pollen extract; EOS, eosinophils; GINIplus, German Infant study on the Influence of Nutrition Intervention plus environmental and genetic influences on allergy development; HDM, house dust mite; IgE, immunoglobulin E; LISA, life-style related factors on the development of the Immune System and Allergies in East and West Germany; M, macrophages; NEU, neutrophils; Th, T helper

This study investigated the relationship between maternal prepregnancy BMI and childhood asthma risk. Mothers were followed throughout their pregnancy, and children were followed up to age 4, 6, or 8 years using electronic medical records. Asthma was assessed at each follow-up age. Higher prepregnancy BMI was associated with a modest increase in childhood asthma risk.Abbreviations: BMI, body mass index; EMR, electronic medical records; LMP, last menstrual period

This study confirms that IL-6-deficient mice are resistant to asthma-protective effect driven by Acinetobacter lwoffii (AL). Downstream of IL-6, the asthma-blocking properties is mediated by IL-10, but not IL-17. In IL-6-deficient mice, exposure to AL increases Muribaculaceae and Sutterellaceae, and decreases Lachnospiraceae and Bacillaceae, compared to the unexposed mice, restoring the status quo observed in the wild-type littermates mice. In vitro experiments demonstrate modulations in the epigenetic landscape of histone mark H3K27ac at the promoter regions of the Il10 pathway-related genes (Mapk1/3, Stat3, and c-MAF) in the CD4⁺ T-cells cultured with AL-conditioned macrophage supernatant (AL-Mφ). These changes were reversed by anti-IL-6 treatment (AL-Mφ + anti-IL-6) and phenocopy by adding rIL-6 alone.Abbreviations: AL, Acinetobacter lwoffii; AL-Mφ, AL-conditioned macrophage; c-Maf, c-musculoaponeurotic fibrosarcoma transcription factor; IL, interleukin; Il6^−/−, Il6 knockout; Il10^−/−, Il10 knockout; Mφ, macrophages; Mapk1/3, mitogen-activated protein kinase 1/3; rIL-6, recombinant IL-6; Stat3, signal transducer and activator of transcription 3; TNF, tumor necrosis factor; WT, wild-type

Respiratory virome profiles of preschool children were associated with spontaneous cytokine release and stimulated antiviral responses from PBMCs, independent of asthma/allergy status. Prokaryotic (bacteriophage)-type viromes dominated the high spontaneous cytokine release responder cluster. High antiviral responders included more eukaryotic-dominated profiles, while low interferon lambda release correlated with increased presence of Picornaviridae and Siphoviridae.Abbreviations: Bact-DNA, endotoxin-free bacterial DNA; LPS, lipopolysaccharides from E. coli 0111:B4; NGS, next generation sequencing; PBMCs, peripheral blood mononuclear cells; Poly I:C, polyinosinic–polycytidylic acid potassium salt; R848, resiquimod; RV-A, rhinovirus A

In this Phase 1b study of CIndU (ColdU and SD) patients, barzolvolimab, a humanized antibody that inhibits KIT activation by SCF, was well tolerated. Barzolvolimab demonstrated marked, rapid, durable depletion of skin MCs, circulating tryptase, reductions in clinical activity, and significant improvements in disease control and QoL. Barzolvolimab has potential as a therapy for MC-mediated diseases.Abbreviations: CIndU, chronic inducible urticaria; ColdU, cold urticaria; FcR, Fc receptor; Ig, immunoglobulin; KIT, KIT proto-oncogene, receptor tyrosine kinase; MC, mast cell; MRGPRX2, mas-related G protein-coupled receptor-X2; QoL, quality of life; SCF, stem cell factor; SD, symptomatic dermographism

This study characterizes molecular effects of best supportive care only (BSCO) or in combination with intravenous immunoglobulins (IVIG) or cyclosporine A (CSA) in the acute phase of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Serum inflammatory profiles show massive upregulation of type 1 immune response and proinflammatory markers. IVIG-treated patients present different dynamics and most significant proteomic changes in an early phase (Day 5–7). In all treatment groups, type 1−/inflammatory response markers are dampened at Day 21.Abbreviations: BSCO, best supportive care only; CNTNAP2, contactin associated protein 2; CSA, cyclosporine A; IVIG, intravenous immunoglobulins; ITGA11, integrin subunit alpha 11; SCF, stem cell factor; SJS, Stevens-Johnson-Syndrome; TEN, toxic epidermal necrolysis

MRSA induces a broad range of cytokines, while MSSA induces IL-1β and TNF-α. Staphylococcus aureus-induced IL-1β, TNF-α, and IL-6 inhibit ELOVL3, resulting in accumulation of lipids with C14-C18 FAs, while MRSA-induced IL-33 inhibits both ELOVL3 and ELOVL4, concomitantly increasing lipids with C14-C18 FAs and decreasing lipids with FAs ≥ 22. S. aureus-mediated aberrant lipid profiles cause increased TEWL and skin barrier dysfunction.Abbreviations: 3D skin, organotypic skin; ELOVL, fatty acid elongase; FA, fatty acid; IL, interleukin; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; SA, Staphylococcus aureus; TEWL, transepidermal water loss; TNF, tissue necrosis factor

An integrated meta-analysis employing both LEAP (high risk) and EAT (normal risk) individual patient data shows that early introduction of peanut in infancy prevents the development of peanut allergy regardless of presence or severity of eczema, ethnicity and sensitization to peanut. Earlier introduction of peanut before 6 months of age is more effective than later introduction in the prevention of peanut allergy. Causal inference methods accurately estimated the efficacy of this strategy while addressing the problems of poor adherence in the intention-to-treat analyses and biases in the per-protocol analyses.Abbreviations: EAT, enquiring about tolerance; ITT, intention to treat; LEAP, learning early about allergy; PP, per protocol

This study analyzes the lipidomic and transcriptomic profile of platelets in patients with mild and severe allergy. The lipidomic profile of platelets form severe allergic patients shows high levels of ceramides, phosphoinositols, phosphocholines, and sphingomyelins and low levels of arachidonic acid. Transcriptomics reveals a higher expression of platelet activation genes and the alteration of IL-17, MAPK, TLR, and NLR pathways in the severe phenotype, which was validated by P-Selectin and IL-17 AF protein quantification.Abbreviations: ALOX12, arachidonate 12-lipoxygenase; CD40L, CD40 ligand; CPM, counts per millon; IL, interleukin; ITGB3, integrin subunit beta 3; −Log(P), −Logarithm in base 10 of P value; MAPK, mitogen-activated protein kinase; NLR, NOD-like receptor; PPBP, pro-platelet basic protein; SELP, selectin P; TLR, Toll-like receptor

Increased vascular permeability due to BK is the leading cause of the C1-INH-HAE. CU06-1004 oral administration significantly alleviated vascular hyperpermeability in C1-INH-HAE murine in vivo model by protecting vascular integrity. CU06-1004 protected the endothelial barrier from BK-induced interendothelial cell gap formation by inhibiting VE-cadherin phosphorylation and stress fiber formation.Abbreviations: BK, bradykinin; C1-INH, C1 esterase inhibitor; C1-INH-HAE, hereditary angioedema caused by C1 esterase inhibitor deficiency; CTRL, control; CU06-1004, endothelial dysfunction blocker; EC, endothelial cell; F-actin, filamentous actin; HMW kininogen, high-molecular-weight kininogen; KO, knock-out; MLC, myosin light chain; Src, non-receptor tyrosine kinase; VE-cadherin, vascular endothelial cadherin; WT, wild type

This study evaluates the utility of KITD816V mutational status in blood (vs. bone marrow) for the diagnostic screening of SM and MCAS patients, having a high specificity but a limited sensitivity in patients presenting with clonal MCAS without skin lesions. Assessment of KITD816V in blood-purified myeloid cell populations increases the diagnostic sensitivity of this mutation in 61% of patients. Further, an unstable (decrease or increase) KIT mutation cell burden during follow-up is a strong predictor of shortened progression-free survival in SM.Abbreviations: BM, bone marrow; KITD816V, somatic mutation in codon 816 of the stem cell growth factor receptor gene; MC, mast cell; MCAS, mast cell activation syndromes; No., number; PFS, progression-free survival; SM, systemic mastocytosis