Epigenetics: An opportunity to shape innate and adaptive immune responses.

Epigenetics connects genetic and environmental factors: it includes DNA methylation, histone post-translational modifications and the regulation of chromatin accessibility by non-coding RNAs, all of which control constitutive or inducible gene transcription. This plays a key role in harnessing the transcriptional programs of both innate and adaptive immune cells due to its plasticity and environmental-driven nature, piloting myeloid and lymphoid cell fate decisions with no change in their genomic sequence. In particular, epigenetic marks at the site of lineage-specific transcription factors and maintenance of cell type-specific epigenetic modifications, referred to as 'epigenetic memory', dictate cell differentiation, cytokine production and functional capacity following repeated antigenic exposure in memory T cells.

Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network.

Ataxia telangiectasia (AT) is a rare neurodegenerative genetic disorder due to bi-allelic mutations in the Ataxia Telangiectasia Mutated (ATM) gene. The aim of this paper is to better define the immunological profile over time, the clinical immune-related manifestations at diagnosis and during follow-up, and to attempt a genotype-phenotype correlation of an Italian cohort of AT patients. Retrospective data of 69 AT patients diagnosed between December 1984 and November 2019 were collected from the database of the Italian Primary Immunodeficiency Network.

SARS-CoV-2 Infection in the Immunodeficient Host: Necessary and Dispensable Immune Pathways.

Since its outbreak in late December 2019 in Wuhan, coronavirus disease 2019 pandemic has posed a therapeutic challenge for the world population, with a plenty of clinical pictures and a broad spectrum of severity of the manifestations. In spite of initial speculations on a direct role of primary or acquired immune deficiency in determining a worse disease outcome, recent studies have provided evidence that specific immune defects may either serve as an experimentum naturae entailing this risk or may not be relevant enough to impact the host defense against the virus. Taken together, these observations may help unveil pathogenetic mechanisms of the infection and suggest new therapeutic strategies.

Complement system network in cell physiology and in human diseases.

The complement system is a multi-functional system representing the first line host defense against pathogens in innate immune response, through three different pathways. Impairment of its function, consisting in deficiency or excessive deregulated activation, may lead to severe systemic infections or autoimmune disorders. These diseases may be inherited or acquired.

CD4 T Cell Defects in a Mulibrey Patient With Specific Mutations.

Mulibrey (muscle-liver-brain-eye) syndrome (MUL) is an autosomal recessive disorder caused by mutations in the () gene, encoding for TRIM37 a member of the TRIM E3 ubiquitin ligase protein family. MUL patients are characterized by growth retardation, dysmorphic features, and a wide range of abnormalities affecting different organs. However, T-cell abnormalities have not been observed in MUL subjects, to date.

In Ataxia-Telangiectasia, Oral Betamethasone Administration Ameliorates Lymphocytes Functionality through Modulation of the IL-7/IL-7Rα Axis Paralleling the Neurological Behavior: A Comparative Report of Two Cases.

Ataxia-Telangiectasia (A-T) is characterized by cerebellar neurodegeneration and immunodeficiency. Recent studies suggest that very low glucocorticoids (GCs) doses may help improve A-T neurological phenotype in some patients. Interestingly, in GCs studies an unexpected improvement of lymphocytes proliferation in some A-T patients has been observed.

Clinical, Immunological, and Functional Characterization of Six Patients with Very High IgM Levels.

Very high IgM levels represent the hallmark of hyper IgM (HIGM) syndromes, a group of primary immunodeficiencies (PIDs) characterized by susceptibility to infections and malignancies. Other PIDs not fulfilling the diagnostic criteria for HIGM syndromes can also be characterized by high IgM levels and susceptibility to malignancies. The aim of this study is to characterize clinical phenotype, immune impairment, and pathogenic mechanism in six patients with very high IgM levels in whom classical HIGM syndromes were ruled out.

Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network.

Severe combined immunodeficiencies (SCIDs) are a group of inborn errors of the immune system, usually associated with severe or life-threatening infections. Due to the variability of clinical phenotypes, the diagnostic complexity and the heterogeneity of the genetic basis, they are often difficult to recognize, leading to a significant diagnostic delay (DD). Aim of this study is to define presenting signs and natural history of SCID in a large cohort of patients, prior to hematopoietic stem cell or gene therapies.

Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis.

FOXN1 is the master regulatory gene of thymic epithelium development. FOXN1 deficiency leads to thymic aplasia, alopecia, and nail dystrophy, accounting for the nude/severe combined immunodeficiency (nu/SCID) phenotype in humans and mice. We identified several newborns with low levels of T cell receptor excision circles (TRECs) and T cell lymphopenia at birth, who carried heterozygous loss-of-function FOXN1 variants.

Effectiveness and safety of a product containing diosmin, coumarin, and arbutin (Linfadren®) in addition to complex decongestive therapy on management of breast cancer-related lymphedema.

Purpose: To assess the effectiveness and safety of a product containing diosmin, coumarin, and arbutin (Linfadren®) in addition to complex decongestive therapy (CDT) on the management of patients with a breast cancer-related lymphedema (BCRL).

Methods: Fifty outpatients (average age of 56.2 ± 2.

Water safety in healthcare facilities. The Vieste Charter.

The Study Group on Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health (GISIO-SItI) and the Local Health Authority of Foggia, Apulia, Italy, after the National Convention "Safe water in healthcare facilities" held in Vieste-Pugnochiuso on 27-28 May 2016, present the "Vieste Charter", drawn up in collaboration with experts from the National Institute of Health and the Ministry of Health. This paper considers the risk factors that may affect the water safety in healthcare facilities and reports the current regulatory frameworks governing the management of installations and the quality of the water. The Authors promote a careful analysis of the risks that characterize the health facilities, for the control of which specific actions are recommended in various areas, including water safety plans; approval of treatments; healthcare facilities responsibility, installation and maintenance of facilities; multidisciplinary approach; education and research; regional and national coordination; communication.

Unbalanced Immune System: Immunodeficiencies and Autoimmunity.

Increased risk of developing autoimmune manifestations has been identified in different primary immunodeficiencies (PIDs). In such conditions, autoimmunity and immune deficiency represent intertwined phenomena that reflect inadequate immune function. Autoimmunity in PIDs may be caused by different mechanisms, including defects of tolerance to self-antigens and persistent stimulation as a result of the inability to eradicate antigens.

Deep neck abscess due to Acinetobacter baumannii infection.

Acinetobacter baumannii strains are isolated in up to 1% of nosocomial infections mostly from intensive care units immunocompromised patients and are associated with high mortality rates. A baumannii infections include pneumonia, urinary tract infection, endocarditis, skin and soft-tissue infections, surgical-site infection, meningitis, osteomyelitis, and septicemia. We report an extremely rare case of deep neck abscess due to multidrug-resistant A baumannii infection.

Maternal morphine alters parvalbumin immunoreactivity patterns in neonatal mouse brain.

The influence of chronic maternal morphine on the parvalbumin immunoreactive patterns in developing mouse brain was studied. Female Swiss mice were administered daily saline or morphine (30 or 60 mg/kg) for a period of 7 days before mating, gestation, and 21 days postpartum. Their pups were sacrificed on postnatal day 18 and the brains were examined histologically and immunohistochemically for parvalbumin-positive neurons.

Chronic morphine alters calbindin D-28k immunostaining patterns in mouse forebrain.

The influence of chronic morphine treatment on the brain of adult mouse has been studied. Female Swiss mice were daily administered saline or morphine (30 or 60 mg/kg body weight) for a period comprising 7 days before mating, during gestation and until 21 days post-partum. Their brains were then perfusion-fixed and examined for histology and calbindin D-28k protein-immunoreactivity.