Immune Development in Early Life (IDEaL) longitudinal cohort study protocol: Identifying biomarkers of vaccine responsiveness, respiratory infection, and asthma.

Background: Early-life immune development is a critical factor in predicting the risk of childhood respiratory infections, asthma, and poor vaccine responses. Identifying immune endotypes that predispose children to these conditions could lead to the development of predictive biomarkers and early interventions, potentially improving long-term health outcomes. The IDEaL (Immune Development in Early Life)-Rome prospective pediatric cohort, based at Children's Hospital Bambino Gesù (Rome, Italy), is part of a National Institutes of Health/National Institute of Allergy and Infectious Diseases-supported longitudinal observational study.

Longitudinal Meta-cohort study protocol using systems biology to identify vaccine safety biomarkers.

The International Network of Special Immunization Services (INSIS) was established to investigate the causes and risk factors of rare adverse events following immunizations (AEFIs) and develop immunization strategies for mitigating or preventing risk for individuals with prior AEFIs or at risk of AEFIs. INSIS integrates clinical data with multi-omic technologies (e.g.

Factors associated with and kinetics of anti-IFN-α autoantibodies in deficiency.

Background: Autoantibodies against IFN-α (anti-IFN-α) have been reported in recombinase activating gene (RAG) deficiency, attributed to impaired central and peripheral T-cell/B-cell tolerance. However, the clinical features, especially viral infections, associated with these autoantibodies at baseline, their kinetics over time, and their response to hematopoietic cell transplantation are not well defined.

Objective: We described the clinical and immunologic findings linked to anti-IFN-α IgG in RAG deficiency and tracked its kinetics longitudinally, including in those who underwent hematopoietic cell transplantation.

Etiopathogenesis of "Bladder Outlet Obstruction" in the Female - Inability of Pelvic Muscles to Sufficiently Open Urethra.

Background: Historically, opening the bladder neck and urethra for evacuation has been solely by detrusor contraction with "urethral relaxation."

Summary: We present a change in thinking based on experimental research and clinical practice, human and animal: the urethra is opened externally immediately prior to detrusor contraction by posterior pelvic floor muscles contracting against competent uterosacral ligaments (USLs). A binary feedback control system (EITHER open OR closed) with neurological and peripheral musculo-ligamentous components is presented.

Mathematical modeling and mechanisms of HIV latency for personalized anti latency therapies.

Combination antiretroviral therapy controls human immunodeficiency virus-1 (HIV) but cannot eradicate latent proviruses in immune cells, which reactivate upon treatment interruption. Anti-latency therapies like "shock-and-kill" are being developed but are yet to succeed due to the complexity of latency mechanisms. This review discusses recent advances in understanding HIV latency via mathematical modeling, covering key regulatory factors and models to predict latency reversal, highlighting gaps to guide future therapeutic approaches.

Distinct viral reservoirs and immune signatures in individuals on long-term antiretroviral therapy with perinatally acquired HIV-1.

Early initiation of antiretroviral therapy (ART) following HIV-1 infection restricts the size of the latent reservoir, following both horizontal and vertical infections. Here, we comprehensively profile the reservoirs and immunological milieus of nine young adults who acquired HIV-1 perinatally and remained on suppressive long-term ART (median: 20 years) since infancy (LeukoHIV cohort). Genome-intact reservoirs are markedly smaller compared to a cohort of adults on suppressive ART started in adulthood, with some LeukoHIV individuals characterized by an absence or near absence of intact proviruses in up to a billion peripheral blood mononuclear cells (PBMCs).

Innate Lymphoid Cell Phenotypic and Functional Alterations in Patients With Systemic Juvenile Idiopathic Arthritis.

Objective: Systemic juvenile idiopathic arthritis (sJIA) is a chronic childhood disease classically attributed to innate immune cell dysregulation. This study aimed to elucidate the role of innate lymphoid cells (ILCs), including natural killer (NK) cells and helper-ILCs (hILCs), in sJIA during clinically inactive disease (CID) through phenotypic and functional analysis.

Methods: Peripheral ILCs from children with sJIA during CID receiving interleukin-1 (IL-1) inhibitors (n = 40) were analyzed by flow cytometry and compared to 23 healthy children (HC) and 22 patients with unrelated autoinflammatory diseases taking IL-1 inhibitors.

Network analysis reveals protein modules associated with childhood respiratory diseases.

Background: The first year of life represents a dynamic immune development period that impacts the risk of developing respiratory-related diseases, including asthma, recurrent infections, and eczema. However, the role of immune-mediating proteins in childhood respiratory diseases is not well characterized in early life.

Objective: The objective of this study was to investigate relationships between protein profiles at age 1 year and respiratory-related diseases by age 6 years, including asthma, recurrent wheeze, respiratory infections, and eczema.

Gut Microbial Signatures Associated with Cryptosporidiosis: A Case Series.

spp. are zoonotic protozoan parasites with a global prevalence, with both gastrointestinal and pulmonary involvement. Though symptoms can often be relatively mild, they can become severe and even fatal in children under five, the elderly, and in immunocompromised individuals, making cryptosporidiosis a leading cause of morbidity and mortality in fragile populations.

Social-support buffers the effect of internalized homonegativity on intrusive sexual thoughts/behaviors.

Objective: Among gay, bisexual, and other men who have sex with men, intrusive sexual thoughts/behaviors (i.e., distress about one's sexual urges or behaviors) are associated with depression and engagement in behavior that increases the risk for sexually transmitted infections (STIs).

Pre-vaccination immune markers predict response to BNT162b2 mRNA vaccine in vulnerable groups - The CONVERS project, report from a pediatric tertiary hospital.

Background: Whereas several studies have demonstrated the long-term immunogenicity of BNT162b2 vaccine in healthy adults, little evidence was provided in vulnerable populations (VPs) with generally low ability to respond to immunizations. We aimed to identify pre-vaccination immune phenotype and transcriptional signatures in B and T-cell subsets associated with immune response and long-term maintenance upon SARS-CoV-2 vaccination in VPs.

Methods: A cohort of VPs (N = 169) including solid organ transplant recipients (SOT; N = 35), Inflammatory Bowel Disease (N = 31), Down Syndrome (N = 42), people living with HIV (N = 36), primary immune deficiencies (N = 25) and healthy controls (N = 37) were enrolled in the CONVERS Study.

Shielding the immunocompromised: COVID-19 prevention strategies for patients with primary and secondary immunodeficiencies.

The COVID-19 pandemic has significantly impacted immunocompromised patients, particularly those with inborn errors of immunity (IEI), transplant recipients, hematologic malignancies, and those undergoing treatment with immunosuppressive biologics and medications. These patients face an elevated risk of experiencing severe or even fatal consequences following SARS-CoV-2 infections. Vaccination is the primary defense against COVID-19; however, immune responses following immunization are often suboptimal in these patients, with variable specific humoral response rates.

Distinct pro-inflammatory/pro-angiogenetic signatures distinguish children with Long COVID from controls.

Background: Recent proteomic studies have documented that Long COVID in adults is characterized by a pro-inflammatory signature with thromboinflammation. However, if similar events happen also in children with Long COVID has never been investigated.

Methods: We performed an extensive protein analysis of blood plasma from pediatric patients younger than 19 years of age Long COVID and a control group of children with acute COVID-19, MIS-C, and healthy controls resulted similar for sex distribution and age.

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.

Safety of Nirmatrelvir-Ritonavir Administration in Children With Immunodeficiency and/or Comorbidities With SARS-CoV-2 Infection: A Retrospective Clinical Report.

Introduction: Despite the generally mild course of COVID-19 in children, immunocompromised patients may experience complications or severe infection. This study reports the clinical outcomes of pediatric patients treated with nirmatrelvir and ritonavir (N/R) for SARS-CoV-2 infection.

Methods: We retrospectively reported the data of children with any immunodeficiency with COVID-19 who received N/R treatment between March 2022 and June 2023 at the Bambino Gesù Children's Hospital.

Monocytes across life span in HIV infection: lights and shadows.

Purpose Of Review: This review highlights the role of monocytes in the pathogenesis of HIV-1 infection, focusing on their involvement in the inflammatory response and their function as viral targets and long-term reservoirs.

Recent Findings: Monocytes have been categorized into three subsets: classical, intermediate, and nonclassical, each with distinct functional characteristics. Advances in genetic sequencing technologies have enabled a more in-depth exploration of the phenotypic and functional variations among these subsets, particularly in the context of HIV.

Biomarkers of vaccine safety and efficacy in vulnerable populations: Lessons from the fourth international precision vaccines conference.

Vaccination has been a cornerstone of public health, substantially reducing the global burden of infectious diseases, notably evident during the COVID-19 pandemic caused by SARS-CoV-2. However, vulnerable populations (VPs), including those in extreme age groups and those with underlying health conditions, have borne a disproportionate burden of morbidity and mortality from infectious diseases. Understanding vaccine immunogenicity in these populations is crucial for developing effective vaccines.

The BNT162b2 mRNA vaccine demonstrates reduced age-associated T1 support and .

mRNA vaccines demonstrate impaired immunogenicity and durability in vulnerable older populations. We hypothesized that human modeling and proteomics could elucidate age-specific mRNA vaccine actions. BNT162b2-stimulation changed the plasma proteome of blood samples from young (18-50Y) and older adult (≥60Y) participants, assessed by mass spectrometry, proximity extension assay, and multiplex.

Early inflammation as a footprint of increased mortality risk in infants living with HIV from three African countries.

In this work our aim was to identify early biomarkers in plasma samples associated with mortality in children with perinatal HIV treated early in life, to potentially inform early intervention targeting this vulnerable group. 20/215 children (9.3%) with perinatal HIV, enrolled within 3 months of age died prematurely within the first year of the study, despite early ART initiation.

Multi-modal immune dynamics of pre-COVID-19 Kawasaki Disease following intravenous immunoglobulin.

Despite progress, the molecular mechanisms underlying Kawasaki Disease (KD) and intravenous immunoglobulin's (IVIG) ability to mitigate the inflammatory process remain poorly understood. To characterize this condition, plasma proteomic profiles, flow cytometry, and gene expression of T cell subsets were investigated in longitudinal samples from KD patients and compared with two control groups. Systems-level analysis of samples in the acute phase revealed distinctive inflammatory features of KD, involving mainly Th-1 and Th-17 mediators and unveiled a potential disease severity signature.