Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Dysregulated specific IgE production to bystander foods in children with peanut allergy but not egg allergy.

Background: Food specific immunoglobulin E (sIgE) levels are associated with the development of allergic responses and are used in the clinical evaluation of food allergy. Food sIgG4 levels have been associated with tolerance or clinical nonresponsiveness, particularly in interventional studies.

Objective: We aimed to characterize food-specific antibody responses and compare responses with different foods in food allergy.

A 2-Year-Old Child with Alazami Syndrome with Newly Reported Findings of Immune Deficiency, Periventricular Nodular Heterotopia, and Stroke; Broadening the Phenotype of Alazami.

Alazami syndrome is a rare autosomal recessive neurodevelopmental disorder due to loss-of-function variants in the La ribonucleoprotein 7 gene. Children with Alazami syndrome are most often affected by a combination of primordial dwarfism, intellectual disability, and distinctive facial features. Previous cases have been primarily found in consanguineous families from the Middle East, Asia, and North Africa.

Rheumatologic diseases in patients with inborn errors of immunity in the USIDNET registry.

There is a gap in clinical knowledge regarding associations between specific inborn errors of immunity (IEIs) and rheumatologic diseases. This study reports the frequency of rheumatologic conditions in a large cohort of patients with IEI using the USIDNET (United States Immunodeficiency Network) registry. We used the USIDNET registry to conduct the analysis.

Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score.

Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant.

Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant.

Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices.

The infant and toddler with wheezing.

Recurrent wheezing is common in young infants and toddlers, with 50% of all children having at least one wheezing episode in the first 6 years of life. Initial wheezing episodes in young children often are linked to respiratory infections due to viral pathogens, such as respiratory syncytial virus, human rhinovirus, human metapneumovirus, and influenza virus. Bacterial colonization of the neonatal airway also may be significant in the late development of recurrent wheeze and asthma.

Classification of asthma.

Asthma is a chronic inflammatory disorder of the airways that results, physiologically, in hyperreactivity and, clinically, in recurrent episodes of wheezing, chest tightness, or coughing. Airway inflammation, smooth-muscle contraction, epithelial sloughing, mucous hypersecretion, bronchial hyperresponsiveness, and mucosal edema contribute to the underlying pathophysiology of asthma. Diagnostic tests such as methacholine or mannitol challenges or spirometry (pre- and postbronchodilator responses) help to identify such underlying pathophysiology assessments of bronchial hyperreactivity and lung mechanics but are imperfect and, ultimately, must be viewed in the context of a patient's clinical presentation, including response to pharmacotherapy.

Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis.

FOXN1 is the master regulatory gene of thymic epithelium development. FOXN1 deficiency leads to thymic aplasia, alopecia, and nail dystrophy, accounting for the nude/severe combined immunodeficiency (nu/SCID) phenotype in humans and mice. We identified several newborns with low levels of T cell receptor excision circles (TRECs) and T cell lymphopenia at birth, who carried heterozygous loss-of-function FOXN1 variants.

Lysophosphatidic acid stimulates epidermal growth factor-family ectodomain shedding and paracrine signaling from human lung fibroblasts.

Lysophospatidic acid (LPA) is a bioactive lipid mediator implicated in tissue repair and wound healing. It mediates diverse functional effects in fibroblasts, including proliferation, migration and contraction, but less is known about its ability to evoke paracrine signaling to other cell types involved in wound healing. We hypothesized that human pulmonary fibroblasts stimulated by LPA would exhibit ectodomain shedding of epidermal growth factor receptor (EGFR) ligands that signal to lung epithelial cells.