First Case of Patient With Two Homozygous Mutations in MYD88 and CARD9 Genes Presenting With Pyogenic Bacterial Infections, Elevated IgE, and Persistent EBV Viremia

We described for the first time a female patient with the simultaneous presence of two homozygous mutations in MYD88 and CARD9 genes presenting with pyogenic bacterial infections, elevated IgE, and persistent EBV viremia. In addition to defective TLR/IL1R-signaling, we described novel functional alterations into the myeloid compartment. In particular, we demonstrated a defective production of reactive oxygen species exclusively in monocytes upon E. coli stimulation, the inability of immature mono-derived DCs (iDCs) to differentiate into mature DCs (mDCs) and the incapacity of mono-derived macrophages (MDMs) to resolve BCG infection in vitro. Our data do not provide any evidence for digenic inheritance in our patient, but rather for the association of two monogenic disorders. This case illustrates the importance of using next generation sequencing (NGS) to determine the most accurate and early diagnosis in atypical clinical and immunological phenotypes, and with particular concern in consanguineous families. Indeed, besides the increased susceptibility to recurrent invasive pyogenic bacterial infections due to MYD88 deficiency, the identification of CARD9 mutations underline the risk of developing invasive fungal infections emphasizing the careful monitoring for the occurrence of fungal infection and the opportunity of long-term antifungal prophylaxis

Susceptibility to allergy in adoptive children: a cross-sectional study at “Bambino Gesù Children’s Hospital”

Abstract Background Prevalence of allergy has steeply increased during the past few decades, particularly in high-income countries. The development of atopy could present different characteristics in internationally adopted children with regard to incidence, specific patterns of allergies and timing of occurrence. We aimed to investigate the occurrence of allergic diseases among adopted children in Italy. Methods We collected demographic information, preadoption immunization data, infectious diseases screening results, immunological status, and performed hematological and biochemical tests according to a standardized protocol in 108 adopted children. Results At initial visit (mean age was 5.7 ± 3.2 years), 48 children displayed elevated total serum IgE levels with a prevalence of 56.5% (95%CI: 0.45; 0.67). The prevalences of children screened positive for one or more food allergens and inhalants were 30.1% (95%CI: 19.9%; 42.0%) and 34.3% (95%CI: 23.3%; 46.6%) respectively, only 9 children exhibited abnormal absolute eosinophil counts, 23 (21.3%) had a parasitic infection and 60 (55.6%) had received at least one dose of vaccine. Conclusions Children without medical records or with a past medical history suggestive of atopy should perform a thorough allergy evaluation at the time of adoption. Our study offers also a glimpse at the vaccination status and immune-allergic profiles of recent migrant children in Italy

Low-dose antibiotic prophylaxis induces rapid modifications of the gut microbiota in infants with vesicoureteral reflux

Background and Objectives: Maturation of the gut microbiota (GM) in infants is critically affected by environmental factors, with potential long-lasting clinical consequences. Continuous low-dose antibiotic prophylaxis (CAP) is the standard of care for children with vesicoureteral reflux (VUR), in order to prevent recurrent urinary tract infections. We aimed to assess short-term GM modifications induced by CAP in infants. Methods: We analyzed the GM structure in 87 infants (aged 1-5 months) with high-grade VUR, previously exposed or naïve to CAP. Microbial DNA was extracted from stool samples. GM profiling was achieved by 16S rRNA gene-based next-generation sequencing. Fecal levels of short- and branched-chain fatty acids were also assessed. Results: 36/87 patients had been taking daily CAP for a median time of 47 days, while 51/87 had not. In all patients, the GM was predominantly composed by Bifidobacteriaceae and Enterobacteriaceae. Subgroup comparative analysis revealed alterations in the GM composition of CAP-exposed infants at phylum, family and genus level. CAP-exposed GM was enriched in members of Enterobacteriaceae and Bacteroidetes, especially in the genera Bacteroides and Parabacteroides, and showed a trend toward increased Klebsiella, often associated with antibiotic resistance. In contrast, the GM of non-CAP children was mostly enriched in Bifidobacterium. No differences were found in fatty acid levels. Conclusions: In infants with VUR, even a short exposure to CAP definitely alters the GM composition, with increased relative abundance of opportunistic pathogens and decreased proportions of health-promoting taxa. Early low-dose antibiotic exposure might bear potential long-term clinical risks

Low-Dose Antibiotic Prophylaxis Induces Rapid Modifications of the Gut Microbiota in Infants With Vesicoureteral Reflux

none21siBackground and Objectives: Maturation of the gut microbiota (GM) in infants is critically affected by environmental factors, with potential long-lasting clinical consequences. Continuous low-dose antibiotic prophylaxis (CAP) is the standard of care for children with vesicoureteral reflux (VUR), in order to prevent recurrent urinary tract infections. We aimed to assess short-term GM modifications induced by CAP in infants. Methods: We analyzed the GM structure in 87 infants (aged 1-5 months) with high-grade VUR, previously exposed or naïve to CAP. Microbial DNA was extracted from stool samples. GM profiling was achieved by 16S rRNA gene-based next-generation sequencing. Fecal levels of short- and branched-chain fatty acids were also assessed. Results: 36/87 patients had been taking daily CAP for a median time of 47 days, while 51/87 had not. In all patients, the GM was predominantly composed by Bifidobacteriaceae and Enterobacteriaceae. Subgroup comparative analysis revealed alterations in the GM composition of CAP-exposed infants at phylum, family and genus level. CAP-exposed GM was enriched in members of Enterobacteriaceae and Bacteroidetes, especially in the genera Bacteroides and Parabacteroides, and showed a trend toward increased Klebsiella, often associated with antibiotic resistance. In contrast, the GM of non-CAP children was mostly enriched in Bifidobacterium. No differences were found in fatty acid levels. Conclusions: In infants with VUR, even a short exposure to CAP definitely alters the GM composition, with increased relative abundance of opportunistic pathogens and decreased proportions of health-promoting taxa. Early low-dose antibiotic exposure might bear potential long-term clinical risks.openMorello W.; D'Amico F.; Serafinelli J.; Turroni S.; Abati I.; Fiori J.; Baskin E.; Yalcinkaya F.; Jankauskiene A.; Pennesi M.; Zurowska A.; Becherucci F.; Drozdz D.; Mekahli D.; Krzemien G.; La Scola C.; Taranta-Janusz K.; Mehls O.; Schaefer F.; Candela M.; Montini G.Morello W.; D'Amico F.; Serafinelli J.; Turroni S.; Abati I.; Fiori J.; Baskin E.; Yalcinkaya F.; Jankauskiene A.; Pennesi M.; Zurowska A.; Becherucci F.; Drozdz D.; Mekahli D.; Krzemien G.; La Scola C.; Taranta-Janusz K.; Mehls O.; Schaefer F.; Candela M.; Montini G