Plasmin cleavage of β2-glycoprotein I alters its structure and ability to bind to pathogenic antibodies.

Background: β2-Glycoprotein I (β2GPI) is the main autoantigenic target of antiphospholipid syndrome, with antibodies leading to clinical manifestations. There are 2 known structural isomers of β2GPI: a J shape and a circular shape. The transition between these structures is incompletely understood, with the functional implications unknown.

GAD antibodies in neurological disease: a critical evaluation of the utility and treatment implications of GAD antibodies in clinical practice.

Background: The interpretation of antibodies to glutamic acid decarboxylase 65 (GAD-Abs) in neurological practice is challenging. GAD-Abs are not considered directly pathogenic and immunotherapy guidelines are lacking.

Methods: We undertook a single-center retrospective service evaluation of GAD-Abs, documenting clinical features, immunotherapy responses, and outcomes of 335 patients with positive GAD-Abs measured by indirect ELISA between 2012 and 2020.

Treg fitness signatures as a biomarker for disease activity in Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA) is an autoimmune condition characterised by flares of joint inflammation. However, no reliable biomarker exists to predict the erratic disease course. Normally, regulatory T cells (Tregs) maintain tolerance, with altered Tregs associated with autoimmunity.

Inflammatory Monocytes Are Rapidly Recruited to the Post-Ischaemic Liver in Patients Undergoing Liver Transplantation and Cytokines Associated with Their Activation Correlate with Graft Outcomes.

Liver ischaemia-reperfusion (IR) injury remains a major cause of morbidity and mortality following liver transplantation and resection. CD4+ T cells have been shown to play a key role in murine models; however, there is currently a lack of data that support their role in human patients. Data on clinical outcomes and complications were documented prospectively in 28 patients undergoing first elective liver transplant surgery.

Time to start taking time seriously: how to investigate unexpected biological rhythms within infectious disease research.

The discovery of rhythmicity in host and pathogen activities dates back to the Hippocratic era, but the causes and consequences of these biological rhythms have remained poorly understood. Rhythms in infection phenotypes or traits are observed across taxonomically diverse hosts and pathogens, suggesting general evolutionary principles. Understanding these principles may enable rhythms to be leveraged in manners that improve drug and vaccine efficacy or disrupt pathogen timekeeping to reduce virulence and transmission.

Comparative analysis of solvent-based and solvent-free (melting) methods for fabricating 3D-printed polycaprolactone-hydroxyapatite composite bone scaffolds: physicochemical/mechanical analyses and cytocompatibility.

Purpose: The study conducts a comparative analysis between two prominent methods for fabricating composites for bone scaffolds-the (solid) solvent method and the solvent-free (melting) method. While previous research has explored these methods individually, this study provides a direct comparison of their outcomes in terms of physicochemical properties, cytocompatibility, and mechanical strength. We also analyse their workflow and scalability potentials.

Molnupiravir clinical trial simulation suggests that polymerase chain reaction underestimates antiviral potency against SARS-CoV-2.

Molnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication. Molnupiravir reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral RNA levels in three separate trials. We used mathematical models to simulate these trials and closely recapitulated their virologic outcomes.

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.

Enhanced antibody responses in CD19-Cre mice.

CD19-Cre is an important and widely used Cre-lox model for B cell-specific genetic manipulation in murine systems. Mice carrying one allele of CD19-Cre are, at the same time, rendered heterozygote for CD19, a crucial coreceptor of the B cell antigen receptor (BCR). As a result, CD19-Cre mice exhibit diminished expression levels of CD19, with potential, yet insufficiently examined, consequences in B cell activation.

Harmonization of alcohol use data and mortality across a multi-national HIV cohort collaboration.

Background: Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH).

Methods: Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration.

Recommendations for Transitioning Young People with Primary Immunodeficiency Disorders and Autoinflammatory Diseases to Adult Care.

Purpose: Significant improvements in the prognosis for young patients with Primary Immunodeficiency Diseases (PID) and Autoinflammatory Disorders (AID), which together make up the majority of Inborn Errors of Immunity (IEI), have resulted in the need for optimisation of transition and transfer of care to adult services. Effective transition is crucial to improve health outcomes and treatment compliance among patients. Evaluations of existing transition programmes in European health centres identified the absence of disease-specific transition guidelines for PID and AID, as a challenge to the transition process.

Asparagine availability controls germinal center B cell homeostasis.

The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2.

Lack of phosphatidylinositol 3-kinase VPS34 in regulatory T cells leads to a fatal lymphoproliferative disorder without affecting their development.

Regulatory T (Treg) cells are essential for the maintenance of immunological tolerance, yet the molecular components required for their maintenance and effector functions remain incompletely defined. Inactivation of VPS34 in Treg cells led to an early, lethal phenotype, with massive effector T cell activation and inflammation, like mice lacking Treg cells completely. However, VPS34-deficient Treg cells developed normally, populated the peripheral lymphoid organs and effectively supressed conventional T cells .

Reduced response to SARS-CoV-2 vaccination is associated with impaired immunoglobulin class switch recombination in SLE patients.

Introduction: Systemic lupus erythematosus (SLE) patients exhibit B-cell abnormalities. Although there are concerns about reduced antibody responses to SARS-CoV-2 vaccines, detailed data on B-cell-specific responses in SLE remain scarce. Understanding the responsiveness to novel vaccine antigens, and boosters number, is important to avoid unnecessarily prolonged isolation of immunocompromised individuals.

Griscelli Syndrome Type 2: Comprehensive Analysis of 149 New and Previously Described Patients with RAB27A Deficiency.

Griscelli syndrome type 2 (GS2) is a rare, life-threatening immunodysregulatory disorder characterised by impaired cytotoxic activity leading to susceptibility to haemophagocytic lymphohistiocytosis (HLH) and hypopigmentation. We completed a literature review and analysis of clinical data of 149 patients with GS2 including 8 new patients.We identified three founder mutations which show diverse phenotypic profiles (RAB27A c.

How do autoimmune CD4 T cells handle exhaustion?

Chronic antigen exposure is frequently associated with T cell exhaustion. In a recent study, Aljobaily et al. show that pancreatic islet-infiltrating CD4 T cells in mouse autoimmune diabetes may circumvent exhaustion by preserving TCF1 expression.

Posaconazole nanocrystals dry powder inhalers for the local treatment of invasive pulmonary aspergillosis.

Invasive pulmonary aspergillosis poses a significant threat to immunocompromised patients, characterized by high mortality rates. Posaconazole (PSZ), a second-generation triazole antifungal, exhibits broad-spectrum activity but suffers from limited pulmonary concentrations and notable systemic side effects when administered orally or intravenously. This study focuses on optimizing PSZ nanocrystals-agglomerated particles for dry powder inhalers (DPIs) to enhance solubility, dissolution rates, and pulmonary deposition, ultimately improving therapeutic efficacy while minimizing systemic adverse effects.

Composition of the neutralising antibody response predicts risk of BK virus DNAaemia in recipients of kidney transplants.

Background: BK polyomavirus (BKV) DNAaemia occurs in 10% of recipients of kidney transplants, contributing to premature allograft failure. Evidence suggests disease is donor derived. Hypothetically, recipient infection with a different BKV serotype increases risk due to poorer immunological control.

HBV shows different levels of adaptation to HLA class I-associated selection pressure correlating with markers of replication.

Background & Aims: Immune responses by CD8 T cells are essential for control of HBV replication. Although selection of escape mutations in CD8 T-cell epitopes has previously been described in HBV infection, its overall influence on HBV sequence diversity and correlation with markers of HBV replication remain unclear.

Methods: Whole-genome sequencing was applied to HBV isolates from 532 patients with chronic HBV infection and high-resolution HLA class I genotyping.

Health Care Utilisation in a Cohort of Patients with Primary and Secondary Antibody Deficiency in the United Kingdom.

Introduction: This study investigates the frequency of hospital attendances, emergency care attendances and geographical influences on service interaction in cohorts of patients with primary and secondary antibody deficiency, to inform future service planning and delivery.

Methods: The COVID-19 in Antibody Deficiency (COV-AD) study was a United Kingdom study that enrolled 525 participants between April 2021 and September 2022. Data on health care utilisation was extracted from a screening cohort of participants at one participating site (Birmingham, UK).