CD38high/HLA-DR+CD8+ T lymphocytes display pathogen-specific expansion regardless of hemophagocytic lymphohistiocytosis.

The characteristic expansion of T CD38high/HLA-DR+CD8+ lymphocytes observed in hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) proved able to distinguish HLH/MAS from sepsis and systemic juvenile idiopathic arthritis. However, the performance of this marker in differentiating HLH/MAS from other pediatric febrile conditions with similar clinical onset and yet entirely different treatments remains unexplored. CD38high/HLA-DR+CD8+ frequencies measured in the peripheral fresh blood of pediatric patients attended for suspicion of HLH/MAS were retrospectively recorded and clinical characteristics were retrieved. CD38high/HLA-DR+CD8+ frequencies in HLH/MAS patients (15 patients; median: 22.0%, IQR: 11.0-49.0%) were compared with those who presented febrile conditions other-than-HLH (28 patients; median: 13.0%, IQR: 3.9-28.7%; p = 0.24). HLH and non-HLH patients were subsequently regrouped based on the presence of an identified infection (22 patients; median: 27.0%, IQR: 15.2-72.1%) and compared with those without infections (21 patients; median: 7.6%, IQR: 3.7-24.3%; p = 0.0035). CD38high/HLA-DR+CD8+ percentages were significantly higher only in the infection group compared with the noninfection one, with a patent pathogen-specific expansion in Epstein-Barr virus primoinfection and visceral leishmaniasis regardless of the presence of HLH. CD38high/HLA-DR+CD8+ frequencies do not appear as an HLH-specific marker as they naturally expand in other clinical situations that are common in childhood and may mimic HLH initial presentation.

CD38high/HLA-DR+ CD8+ T cells as potential biomarker of hemophagocytic lymphohistiocytosis secondary to visceral Leishmania infection.

Leishmaniasis is a cause of infection associated with hemophagocytic lymphohistiocytosis (HLH). The measurement of the CD8+ CD38high/HLA-DR+ T cells in children presenting with acute onset of shock and multisystem organ failure represents an important parameter to distinguish HLH from sepsis or healthy control. CONCLUSION: We report a case series of 4 Italian children suffering from HLH secondary to visceral Leishmaniasis in which the lymphocyte subset assay suggests a potential role of CD38high/HLA-DR+ CD8+ T cells as HLH diagnostic biomarkers. WHAT IS KNOWN: • Visceral Leishmaniasis is a well-known cause of infection associated with hemophagocytic lymphohistiocytosis (HLH). • The measurement of the CD8+ CD38high/HLA-DR+ T cells in children presenting with acute onset of shock and multisystem organ failure represents an important diagnostically useful parameter to readily distinguish HLH from sepsis or healthy controls. WHAT IS NEW: • We report a case series of 4 Italian children suffering from HLH secondary to visceral Leishmaniasis in which the lymphocyte subset assay suggests a potential role of CD38high/HLA-DR+ CD8+ T cells as HLH diagnostic biomarker. • The flow cytometry assay, performed at the disease onset before starting treatment, revealed a mean percentage value of CD38 cells of 36.95% among CD8+ T cells.

Analysis of a Cohort of 165 Pediatric Patients with Human Bocavirus Infection and Comparison between Mono-Infection and Respiratory Co-Infections: A Retrospective Study.

INTRODUCTION: Human Bocavirus (HBoV) is mainly associated with respiratory tract infections. However, its role as respiratory pathogen is not fully understood for a high co-infection rate in symptomatic patients and a significant HBoV detection rate in asymptomatic subjects. This study aimed to describe a large cohort of children with HBoV infection and to compare HBoV mono-infection and co-infections. METHODS: We retrospectively reviewed data from 165 children admitted to Meyer Children's Hospital IRCCS from March 2022 to March 2023 with the diagnosis of HBoV infection, detected using Reverse Transcription qPCR from nasal swabs. Thereafter, we compared patients with HBoV mono-infection (Group A) and those with HBoV co-infections (Group B) in terms of disease severity, established by the length of stay (LOS), the requirement of Pediatric Intensive Care Unit (PICU), and advanced respiratory support (ARS). RESULTS: The median age was 1.5 years; 80% of patients presented with respiratory symptoms. The discharge rate from the emergency department (ED) within 24 h was 42.4%. Most cases (57.6%) were hospitalized, and 7.3% were admitted to PICU due to respiratory failure. Group A comprised 69 patients, and Group B 96 children (95% viral co-infections, 2% bacterial, 3% viral and bacterial). Group A and Group B were similar in hospitalization rate but differed significantly in LOS (median 3 vs. 5 days) and requirement of PICU admission (0 vs. 12 patients, p < 0.001). Patients with a respiratory disease history (17.5%) showed significantly longer LOS and more necessity of inhaled bronchodilator therapy. CONCLUSIONS: HBoV should be considered a relevant respiratory pathogen especially in viral co-infections. Patients with HBoV co-infections have a higher risk of necessitating advanced respiratory support with more PICU admission and longer LOS; a previous respiratory disease puts them at a higher risk of longer hospitalization.

Expanded Newborn Screening for Inborn Errors of Immunity: The Experience of Tuscany.

BACKGROUND: Inborn errors of immunity (IEIs) include 485 inherited disorders characterized by an increased susceptibility to life-threatening infectious diseases, autoimmunity, and malignant diseases with a high mortality rate in the first years of life. Severe combined immunodeficiency is the most severe of the IEIs, and its detection should be a primary goal in a newborn screening (NBS) program. The term "actionable" has recently been used for all IEIs with outcomes that can be demonstrably improved through early specialized intervention. OBJECTIVE: To evaluate the results of the expanded NBS strategy for IEIs in Tuscany Region (Italy), based on T-cell receptor excision circle, kappa recombining excision circle, and tandem mass-based assays. METHODS: This is a retrospective study collecting data from all infants born in Tuscany from October 10, 2018, to October 10, 2022. Tandem mass assay to identify adenosine deaminase and purine nucleoside phosphorylase deficiency, together with T-cell receptor excision circle and kappa recombining excision circle molecular analysis, was conducted on dried blood spot from the newborns' Guthrie Cards. A new dried blood spot and evaluation by an immunologist were carried out when the results of the first test were outside the diagnostic cutoffs. RESULTS: A total of 94,319 newborns were evaluated. Referral rates for T-cell recombining excision circles (0.031%) and kappa recombining excision circles (0.074%) in this study are in line with the data available in literature. The results from the expanded NBS strategy revealed an incidence rate of 1 per 9431 affected newborns. CONCLUSIONS: This work represents the first description of a sustainable and real-life-based expanded NBS program for IEIs with a high diagnostic incidence facilitating prompt management of identified patients.

Food Protein-induced Enterocolitis Syndrome Due to Cuttlefish in a Child with Anaphylaxis to Crustaceans.

Shellfish is defined as any edible marine invertebrate and refers to crustaceans and mollusks. Crustaceans belong to the phylum Arthropods. Mollusks belong to the phylum Mollusca. This report illustrates a rare case of a 6-year-old girl with challenge-proven acute food protein-induced enterocolitis syndrome (FPIES) to cuttlefish (phylum Mollusca, class Cephalopoda), anaphylaxis to crustaceans (phylum Arthropoda), and tolerance to other mollusks, including clams and mussels (phylum Mollusca, class Bivalvia). The association of IgE-mediated food allergy and acute FPIES seen in this case is rare. To our knowledge, this is the first case of FPIES to cuttlefish reported in a child. This challenge highlights the need for further research into the allergens and mechanisms underpinning FPIES at a molecular level, enabling a better understanding of cross-reactivity patterns and the development of diagnostic and predictive tests to assist in clinical practice.