High Affinity Dimeric Uracil-Based Receptor for the Recognition of Adenine Derivatives through Triplex-like Interactions.

Adenine recognition through triplex-like interactions was explored using clamp-shaped artificial receptor , bearing two uracil units and an extended naphthalene scaffold. The requisite binding mode was confirmed for 9-ethyladenine in CDCl via NMR investigations. Phase-transfer experiments demonstrated that selectively binds adenosine from an aqueous mixture of four ribonucleosides.

Self-reported Clinical Outcomes and Quality of Life in Agammaglobulinemia: the Importance of an Early Diagnosis.

Purpose: Patients with (X-linked) agammaglobulinemia (XLA) suffer from severe, recurrent infections potentially leading to life-threatening complications such as sepsis, meningoencephalitis and chronic lung disease. Early diagnosis and timely treatment can prevent infections and secondary complications, emphasizing a role for early detection of XLA via newborn screening (NBS). Our international multicenter survey study aimed to evaluate self-reported outcomes and parental perspectives in XLA patients to determine whether an early diagnosis is associated with better quality of life (QoL).

A preorganized triarmed bis-triazolylpyridine-calix[4]arene with high affinity and selectivity for minor actinides for nuclear waste treatment.

The incorporation of three terdentate 2,6-bis-triazolyl-pyridine units on a calix[4]arene gives a preorganized lipophilic ligand with enhanced efficiency in binding trivalent actinides over lanthanides. Combined time-resolved laser-induced fluorescence spectroscopy, and 1D and H-N HMQC NMR investigations allowed to propose the structures of the complexes and to provide insights into the actinide selectivity.

Predictive factors for therapeutic response and cluster analysis in syndrome of undifferentiated recurrent fever (SURF).

Introduction: Syndrome of undifferentiated recurrent fever (SURF) refers to a group of recurrent fevers without a clear monogenic cause. Clinical spectrum, treatment response predictors and management strategies remain unclear.

Objective: This study aims to longitudinally analyse a homogeneously selected cohort of 101 SURF patients, to identify factors associated with colchicine resistance and to evaluate the efficacy of interleukin-1 (IL-1) inhibitors.

Early diagnosis of serious bacterial infection in febrile infants using type I interferon signature.

Background: Febrile infants ≤90 days are at high risk of serious bacterial infections, but prompt differentiation between viral and bacterial infections remains a challenge. Host gene expression signatures, particularly those involving the type I interferon (IFN) pathway, show promise as diagnostic tools. This study evaluates the ability of IFN signature to differentiate bacterial from viral infections in this population.

NET Proteomic Profiling Reveals New Pathways Potentially Implicated in Dendritic Cell-Mediated Inflammation in DADA2 Patients.

Purpose: Adenosine deaminase 2 Deficiency (DADA2) is an autoinflammatory disease characterized by systemic vasculopathy, strokes and mild immunodeficiency. Recently NETosis has been implicated in the pathogenesis of Deficiency of Adenosine Deaminase 2. To deep investigate the possible effects of NETs on the immune system we characterized proteomic profile of NETs from DADA2 as compared to HD and Polyarteritis Nodosa (PAN) patients.

Nailfold videocapillaroscopy in patients with deficiency of adenosine deaminase 2 (DADA2): a case-control study.

Background: Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease mainly characterized by the presence of systemic inflammation and vascular manifestations such as vasculitis and early-onset stroke. Raynaud's phenomenon (RP) can occur in up to 22% of DADA2 patients. The aim of this work was to investigate the microvascular status of DADA2 patients by the mean of nailfold videocapillaroscopy (NVC) comparing them with adequate healthy controls (HC) and primary RP patients.

Efficacy of High-Dose Intravenous Anakinra in Pediatric TAFRO Syndrome: Report of Two Cases and Literature Review.

TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly) syndrome is a rare, life-threatening inflammatory condition linked to infections, neoplasms, and idiopathic multicentric Castleman disease. Interleukin (IL)-6 inhibitors are the primary treatment, but refractory cases require alternatives. This study reports the first two pediatric TAFRO cases successfully treated with anakinra, an IL-1 receptor antagonist.

Inherited deficiency of DIAPH1 identifies a DNA double strand break repair pathway regulated by γ-actin.

DNA double strand break repair (DSBR) represents a fundamental process required to maintain genome stability and prevent the onset of disease. Whilst cell cycle phase and the chromatin context largely dictate which repair pathway is utilised to restore damaged DNA, it has been recently shown that nuclear actin filaments play a major role in clustering DNA breaks to facilitate DSBR by homologous recombination (HR). However, the mechanism with which nuclear actin and the different actin nucleating factors regulate HR is unclear.

Type I interferon signature: a quantitative standardized method for clinical application.

Type I Interferon (IFN) induced gene expression analysis ("IFN signature") is employed to categorize pathological conditions that exhibit Type I IFN dysregulation and to direct customized therapeutic strategies. For instance, it is used to differentiate patients with IFN-related inflammation from those with conditions primarily mediated by other cytokines, such as juvenile idiopathic arthritis and periodic fevers. Nevertheless, there is currently no standardized method available for clinical practice, and comparing values at different time points or between centers poses a challenge.

Clinical manifestations, disease penetrance, and treatment in individuals with SOCS1 insufficiency: a registry-based and population-based study.

Background: Suppressor of cytokine signalling 1 (SOCS1) insufficiency is an inborn error of immunity affecting the negative regulation of cytokine and growth factor signalling. We aimed to enhance the understanding of clinical manifestations, disease trajectories, disease penetrance, and the effect of Janus kinase (JAK) inhibition in individuals with SOCS1 insufficiency.

Methods: This study used data from two independent cohorts: the European Society for Immunodeficiencies (ESID) registry and the UK Biobank.

The common HAQ STING allele prevents clinical penetrance of COPA syndrome.

COPA syndrome, an autosomal-dominant inborn error of immunity, is nonpenetrant in ∼20% of individuals, with no known mediators of protection. Recent studies implicate STING in the pathogenesis of COPA syndrome. We show that the common HAQ STING allele mediates complete clinical protection.

Calixarenes meet (TGT) G-quadruplex: Exploring reciprocal interactions to develop innovative biotechnological applications.

This study investigates, for the first time, the ability of calixarene ligands to interact with G-quadruplex (GQ) DNA assemblies, which play a critical role in many biological processes, including gene expression regulation, telomere maintenance, and the surveillance of genome stability and DNA repair mechanisms. Specifically, the interaction between two calix[4]arene compounds, featuring cationic or zwitterionic functional groups on their upper rim, and the parallel tetramolecular (TGT) G-quadruplex used as a model, was analyzed using circular dichroism, NMR, and molecular dynamics simulations. The results revealed that both derivatives interact favorably with the GQ model, inducing aggregation at higher ligand concentrations.

Towards the definition of disease phenotypes in paediatric SAPHO syndrome: a national multicentric study.

Objectives: The objective of this study was to confirm the presence of different disease phenotypes of paediatric SAPHO syndrome (pSAPHO) based on their skin manifestations in a large cohort of Italian patients.

Methods: Patients with pSAPHO were enrolled in the Eurofever Registry and the data retrospectively analysed. The patients were categorized according to their skin manifestations into an acne - hidradenitis suppurativa (Acne-HS) group and a palmoplantar pustulosis - psoriasis vulgaris (PPP-PV) group and were compared with patients without skin manifestations (chronic non-bacterial osteomyelitis, CNO).

Inborn Error of WAS Presenting with SARS-CoV-2-Related Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) has been reported in patients with inborn errors of immunity (IEI), providing insights into disease pathogenesis. Here, we present the first case of MIS-C in a child affected by Wiskott-Aldrich syndrome (WAS) gene mutation, elucidating underlying predisposing factors and the involved inflammatory pathways. Genetic analysis revealed a frameshift truncating variant in the WAS gene, resulting in WAS protein expression between mild and severe forms, despite a clinical phenotype resembling X-linked thrombocytopenia (XLT).

Majeed syndrome: first description in a patient of central-European ancestry.

Objectives: We present the first case of a Majeed syndrome in a girl of central-European ancestry.

Methods: Patient's medical records were reviewed. A next-generation sequencing (NGS) panel for autoinflammatory diseases was performed and the mutation was confirmed by Sanger analysis.

A proposed clinical tool to identify high-risk patients for monogenic lupus: a pilot study.

Objectives: To develop an easy-to-use and efficient clinical score to identify monogenic lupus based on clinical presentations and to stratify patients who may benefit from confirmatory molecular genetic testing.

Methods: A comprehensive literature review identified 55 distinct items across 12 clinical and laboratory domains, narrowed down to the top ten by a panel of 12 expert paediatric rheumatologists with 80% consensus. The proposed score was tested in a pilot study on 10 patients with monogenic lupus and 30 control subjects with various autoimmune and autoinflammatory diseases.

Long-term efficacy of MAS825, a bispecific anti-IL1β and IL-18 monoclonal antibody, in two patients with systemic JIA and recurrent episodes of macrophage activation syndrome.

Introduction: Systemic JIA (sJIA), a multifaceted autoinflammatory disorder, can be complicated by life-threatening conditions such as macrophage activation syndrome (MAS) and interstitial lung disease. The management of these conditions presents a therapeutic challenge, underscoring the need for innovative treatment approaches.

Objectives: To report the possible role of MAS825, a bispecific anti-IL1β and IL-18 monoclonal antibody, in the treatment of multi-drug-resistant sJIA.

Interleukin-1 blockade in patients with Wiskott-Aldrich syndrome: a retrospective multinational case series.

Up to 70% of patients with Wiskott-Aldrich syndrome (WAS) develop autoimmune and inflammatory manifestations. Dysregulation of interleukin 1 (IL-1) may be involved in their pathogenesis, yet there is little evidence on treatment with anti-IL-1 agents in these patients. We conducted a multicenter retrospective analysis of 9 patients with WAS treated with anti-IL-1 agents (anakinra or canakinumab).

Therapeutic Role of HPV Vaccination on Benign HPV-induced Epithelial Proliferations in Immunocompetent and Immunocompromised Patients: Case Study and Review of the Literature.

Human papillomavirus (HPV) vaccination represents a milestone in primary prevention of sexually transmitted infections. However, little is known about its possible effects on already established HPV infections. We report the case of a 9-year-old immunosuppressed girl with refractory warts, successfully treated with the nonavalent-HPV vaccine and review the literature about the therapeutic effects of HPV vaccination on benign HPV-induced epithelial proliferations in immunocompetent and immunosuppressed patients.

SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis.