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.

Durlobactam in combination with β-lactams to combat .

() presents significant clinical challenges. This study evaluated the synergistic effects of a β-lactam and β-lactamase inhibitor combination against and explored the underlying mechanisms. Synergy was assessed through MIC tests and time-kill studies, and binding affinities of nine β-lactams and BLIs to eight target receptors (L,D-transpeptidases [LDT] 1-5, D,D-carboxypeptidase, penicillin-binding protein [PBP] B, and PBP-lipo) were assessed using mass spectrometry and kinetic studies.

Altered Purinergic Signaling and CD8+ T Cell Dysregulation in STAT3 GOF Syndrome.

Signal transduction downstream of activating stimuli controls CD8+ T cell biology, however these external inputs can become uncoupled from transcriptional regulation in Primary Immune Regulatory Disorders (PIRDs). Gain-of-function (GOF) variants in STAT3 amplify cytokine signaling and cause a severe PIRD characterized by early onset autoimmunity, lymphoproliferation, recurrent infections, and immune dysregulation. In both primary human and mouse models of STAT3 GOF, CD8+ T cells have been implicated as pathogenic drivers of autoimmunity.

In Situ, High-Resolution Quantification of CO Uptake Rates via Automated Off-Gas Analysis Illuminates Carbon Uptake Dynamics in Cyanobacterial Cultures.

Quantification of cyanobacterial CO fixation rates is vital to determining their potential as industrial strains in a circular bioeconomy. Currently, however, CO fixation rates are most often determined through indirect and/or low-resolution methods, resulting in an incomplete picture of both dynamic behaviors and total carbon fixation potential. To address this, we developed the "Automated Carbon and CO Experimental Sampling System" (ACCESS); a low-cost system for in situ off-gas analysis that supports the automated acquisition of high-resolution volumetric CO uptake rates from multiple cyanobacterial cultures in parallel.

Implementation of a Pilot Study in Adolescent Health Care Transition Program for Chronic Granulomatous Disease: A Single Institution Experience.

Background: The transition to adult health care is challenging for adolescents and young adults (AYA) with Chronic Granulomatous Disease (CGD). This pilot study aimed to facilitate the learning of AYA with CGD about their health care and to aid in the development of life skills to enhance self-care.

Methods: AYA and caregivers (for participants <18 years of age) completed an adapted Transition Readiness Assessment.

Coinfection of Leprosy and Chronic Mucocutaneous Candidiasis in a Family with STAT1 Gain-of-Function Mutation.

This report documents the first known cases of lepromatous leprosy in patients with chronic mucocutaneous candidiasis (CMC) linked to a gain-of-function mutation in the STAT1 gene. Two related patients, a mother and daughter, who both suffer from CMC and lepromatous leprosy, carry a heterozygous STAT1 mutation (c.821G>A; p.

Outcomes in hematopoetic cell transplantation in the setting of mold infections in patients with chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a disorder of immunity characterized by phagocyte dysfunction. Mold infections in patients with CGD are often severe and disseminated. We present patient characteristics, microbiological data, and outcomes for 26 patients with CGD who received hematopoietic cell transplantation (HCT) or gene therapy-modified cells (GT) between 2008 and 2019, with proven fungal infection either before or during their transplant.

Evolution toward extremely high imipenem resistance in outbreak strains.

Treatment of pulmonary disease requires multiple antibiotics including intravenous β-lactams (e.g., imipenem).

Case Report: p40 deficiency underlying pediatric-onset systemic lupus erythematosus.

Introduction: Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40 deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells.

Genome sequences of human anelloviruses in the , , and genera identified from the female genital tract.

We identified and characterized seven anellovirus genome sequences in the female genital tract through virome metagenomic sequencing of cervicovaginal lavage specimens from women living with HIV in Peru. Phylogenetic and genomic analyses indicate that they belong to three newly proposed , , and genera in the family.

Anti-IL12p40 autoantibodies in a teenage girl with multiple recurrent abscesses.

More frequent among adults, phenocopies may be caused by somatic mutations or anti-cytokine autoantibodies, mimicking the phenotypes of primary immunodeficiencies. A fourteen-year-old girl was referred for a two-year history of weight loss and multiple recurrent abscesses, complicated recurrent pneumonia, pyelonephritis, osteomyelitis, and septic shock, without fever. She had started with nausea, hyporexia, and weight loss, then with abscesses in her hands, knee, ankle, and spleen.

Wastewater and clinical surveillance of respiratory viral pathogens on a university campus.

Areas of dense population congregation are prone to experience respiratory virus outbreaks. We monitored wastewater and clinic patients for the presence of respiratory viruses on a large, public university campus. Campus sewer systems were monitored in 16 locations for the presence of viruses using next generation sequencing over 22 weeks in 2023.

A unified metric of human immune health.

Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls.

Lymphocyte-Directed Immunomodulation Remits Thymoma-Associated Autoimmune Pneumonitis.

Background: Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome.

Objectives: To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation.

Evolution towards extremely high β-lactam resistance in outbreak strains.

Treatment of pulmonary disease requires multiple antibiotics including intravenous β-lactams (e.g., imipenem, meropenem).

Autoantibodies to type I interferons in patients with systemic mastocytosis.

Background: Autoantibodies to type I interferons have been identified in association with a variety of inflammatory and autoimmune diseases. Type I interferons have demonstrated inhibitory effects on mast cell proliferation and degranulation. Systemic mastocytosis (SM) is a disease characterized by increased mast cell burden and mediator release.

Influenza Virus Genomic Surveillance, Arizona, USA, 2023-2024.

Influenza viruses are constantly evolving and are therefore monitored worldwide in the hope to reduce the burden of disease by annual updates to vaccine recommendations. We conducted genomic sequencing of 110 influenza A and 30 influenza B viruses from specimens collected between October 2023 and February 2024 in Arizona, USA. We identified mutations in the hemagglutinin (HA) antigenic sites as well as the neuraminidase (NA) gene in our samples.

Dual β-lactam for treatment of pulmonary in a child.

Treatment of infection presents significant challenges, exacerbated by the emergence of macrolide-resistant strains that necessitate the use of multiple antimicrobials in combination and carry the potential for significant toxic effects. Select dual beta-lactam combinations, with or without beta-lactamase inhibitors, have been shown to be highly active . Herein, we describe a 6-year-old child with underlying mild bilateral lower lobe cylindrical bronchiectatic lung disease who developed pulmonary infection and was treated with a multi-drug regimen including two β-lactam antibiotics, achieving both early clinical and microbiological cure.