Cutaneous granulomatosis and combined immunodeficiency revealing Ataxia-Telangiectasia: a case report

Ataxia-telangiectasia (A-T) is a complex multisystem disorder characterized by progressive neurological impairment, variable immunodeficiency and oculo-cutaneous telangiectasia. A-T is a member of chromosomal breakage syndromes and it is caused by a mutation in the ataxia-telangiectasia mutated (ATM) gene. Because of a wide clinical heterogeneity, A-T is often difficult to diagnose in children

Enhanced Oil Spill Remediation by Adsorption with Interlinked Multilayered Graphene

The performances of an innovative material based on graphene multilayers in a 3D structure similar to expanded graphite, Grafysorber\uae G+ (Directa Plus), have been tested via in field applications on a real contaminated site. Several experimental tests were performed using Grafysorber\uae inside adsorbent devices (booms and pillows) to treat waters polluted by oil. The experimental campaign was carried out with the aim of comparing the performances of Grafysorber\uae with those of polypropylene (PP), which is the material used worldwide in case of water oil spill clean-up activities. The results achieved have confirmed a considerably higher selective adsorption capacity of Grafysorber\uae compared to PP, and configure the new material as a promising alternative to standard materials in enhancing oil spill remediation by selective adsorption

Parental Infertility: Impact of the Quality of the Relation between Parents and Adopted Children

n/

Case report: Neonatal-onset inflammatory bowel disease due to novel compound heterozygous mutations in DUOX2

Very Early Onset Inflammatory Bowel Disease (VEO-IBD) is potentially associated with genetic disorders of the intestinal epithelial barrier or inborn errors of immunity (IEI). Dual oxidase 2 (DUOX2), an H2O2-producing NADPH oxidase expressed at apical enterocyte membranes, plays a crucial role in innate defense response. Biallelic DUOX2 mutations have been described only in two patients with VEO-IBD to date. We report the case of a 1-month-old female infant who presented persistent high C-reactive protein (CRP) levels from birth and anemia. Positive occult blood and very high calprotectin in the stool were detected and abdominal ultrasound showed thickened last ileal loop. Full endoscopy evaluation revealed important colon stenosis with multiple pseudo-polyploidy formations that resulted refractory to steroid therapy, requiring a partial colic resection. Histological examination of biopsy samples showed morphological features of IBD. Whole Exome Sequencing (WES) disclosed compound heterozygous variants in the DUOX2 gene: the pathogenic c.2524C>T; p.Arg842Ter and the variant of uncertain significance (VUS) c.3175C>T; p.Arg1059Cys. Molecular and functional studies showed the presence of mutant DUOX2 in the intestinal epithelium of the patient, albeit with at least 50% decreased catalytic activity. In conclusion, we describe the third patient to date with compound heterozygous variants of DUOX2, responsible for monogenic neonatal-IBD. This case expands the knowledge about Mendelian causes of VEO-IBD and DUOX2 deficiency. We suggest that DUOX2 should be part of the diagnostic evaluation of patients with suspected monogenic VEO-IBD

Partial T cell defects and expanded CD56bright NK cells in an SCID patient carrying hypomorphic mutation in the IL2RG gene

X-linked severe combined immunodeficiency (X-SCID) caused by full mutation of the IL2RG gene leads to T- B+ NK- phenotype and is usually associated with severe opportunistic infections, diarrhea, and failure to thrive. When IL2RG hypomorphic mutation occurs, diagnosis could be delayed and challenging since only moderate reduction of T and NK cells may be present. Here, we explored phenotypic insights and the impact of the p.R222C hypomorphic mutation (IL2RGR222C ) in distinct cell subsets in an 8-month-old patient with atypical X-SCID. We found reduced CD4+ T cell counts, a decreased frequency of naïve CD4+ and CD8+ T cells, and an expansion of B cells. Ex vivo STAT5 phosphorylation was impaired in CD4+ CD45RO+ T cells, yet compensated by supraphysiological doses of IL-2. Sanger sequencing on purified cell subsets showed a partial reversion of the mutation in total CD3+ cells, specifically in recent thymic emigrants (RTE), effector memory (EM), and CD45RA+ terminally differentiated EM (EMRA) CD4+ T cells. Of note, patient's NK cells had a normal frequency compared to age-matched healthy subjects, but displayed an expansion of CD56bright cells with higher perforin content and cytotoxic potential, associated with accumulation of NK-cell stimulatory cytokines (IL-2, IL-7, IL-15). Overall, this report highlights an alteration in the NK-cell compartment that, together with the high disease-phenotype variability, should be considered in the suspicion of X-SCID with hypomorphic IL2RG mutation

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

The Inborn Errors of Immunity—Virtual Consultation System Platform in Service for the Italian Primary Immunodeficiency Network: Results from the Validation Phase

purposeInborn errors of immunity (IEI) represent a heterogeneous group of rare genetically determined diseases. In some cases, patients present with complex or atypical phenotypes, not fulfilling the accepted diagnostic criteria for IEI and, thus, at high risk of misdiagnosis or diagnostic delay. this study aimed to validate a platform that, through the opinion of immunologist experts, improves the diagnostic process and the level of care of patients with atypical/complex IEI.MethodsHere, we describe the functioning of the IEI-Virtual consultation system (VCS), an innovative platform created by the italian Immunodeficiency network (IPINet). resultsIn the validation phase, from January 2020 to June 2021, 68 cases were entered on the IEI-VCS platform. a final diagnosis was achieved in 35/68 cases (51%, 95% CI 38.7 to 64.2). In 22 out of 35 solved cases, the diagnosis was confirmed by genetic analysis. In 3/35 cases, a diagnosis of secondary immunodeficiency was made. In the remaining 10 cases, an unequivocal clinical and immunological diagnosis was obtained, even though not substantiated by genetic analysis. conclusionFrom our preliminary study, the VCS represents an innovative and useful system to improve the diagnostic process of patients with complex unsolved IEI disorders, with benefits both in terms of reduction of time of diagnosis and access to the required therapies. these results may help the functioning of other international platforms for the management of complex cases

Clinical and immunological phenotypes of selective IgM deficiency in children: Results from a multicenter study

background: a few studies assessed the clinical and immunological features of selective IgM deficiency (SIgMD), especially in the pediatric age. we aimed to characterize the clinical and immunological phenotypes of a cohort of pediatric patients with SIgMD according to the different diagnostic criteria available. methods: In this multicenter study, we evaluated pediatric SIgMD patients diagnosed at the pediatric clinic in pavia, Italy, or through the Italian primary Immunodeficiency NETwork (IPINET) and monitored changes in their diagnosis over a time frame that ranges from several months to several years. results: forty-eight patients with SIgMD were included (mean serum IgM: 33 mg/dL). the most common clinical manifestations were recurrent infections (67%) and allergies (48%). subgroup analysis according to SIgMD definition criteria of the european society for Immunodeficiencies (ESID) showed no significant difference in clinical manifestations, also considering the group with additional immunological abnormalities. sixteen patients had long-term follow-up, during which 87% preserved their SIgMD diagnosis, while two patients showed a reduction in IgA in addition to low IgM. conclusions: our data suggest that the identification of a reduction in serum IgM in children should lead to a complete immunological work-up to obtain a comprehensive clinical and immunological characterization of the patient. the follow-up of these patients is fundamental to define the disease evolution and appropriate management