Publications by authors named "Moratto D"

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).

View Article and Find Full Text PDF
Article Synopsis
  • PI4KA-related disorder is marked by a variety of neurological and gastrointestinal issues, including spasticity, developmental challenges, and recurrent infections, with specific attention given to the impact on B-cell function and immunodeficiency in some patients. * -
  • The study involved analyzing 13 patients with PI4KA variants, revealing common traits such as B-cell deficiency and hypogammaglobulinemia, alongside significant changes in B-cell subsets and functioning due to metabolic disruptions. * -
  • Findings indicate that mutations in PI4KA lead to disturbances in lipid production and metabolic pathways in B cells, fostering mitochondrial dysfunction and abnormal immune responses, suggesting a critical role of PI4KA in B-cell differentiation and health. *
View Article and Find Full Text PDF
Article Synopsis
  • The STAT1 gain-of-function syndrome leads to chronic mucocutaneous candidiasis and can also cause various other infections, autoimmune issues, and malignancies due to severe lymphopenia.
  • In a study of seven patients with this condition, it was found that increased T lymphocyte apoptosis occurs, especially when stimulated, and treatment with the JAK inhibitor ruxolitinib showed promise in reducing this apoptosis and improving lymphopenia.
  • The findings suggest that JAKinib therapy could be beneficial for treating not only chronic candidiasis and lymphopenia but also for managing increased interferon responses in patients with autoimmune or autoinflammatory symptoms.
View Article and Find Full Text PDF

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt MHCII type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota-specific Tregs.

View Article and Find Full Text PDF

Biallelic KARS1 mutations cause KARS-related diseases, a rare syndromic condition encompassing central and peripheral nervous system impairment, heart and liver disease, and deafness. KARS1 encodes the t-RNA synthase of lysine, an aminoacyl-tRNA synthetase, involved in different physiological mechanisms (such as angiogenesis, post-translational modifications, translation initiation, autophagy and mitochondrial function). Although patients with immune-hematological abnormalities have been individually described, results have not been collectively discussed and functional studies investigating how KARS1 mutations affect B cells have not been performed.

View Article and Find Full Text PDF

Granulomatous lymphocytic interstitial lung disease (GLILD) represents a fatal immune dysregulatory complication in common variable immunodeficiency (CVID). Evidence-based diagnostic guidelines are lacking, and GLILD treatment consists in immunosuppressive drugs; nonetheless, therapeutical strategies are heterogeneous and essentially based on experts' opinions and data from small case series or case reports.We aimed to evaluate the efficacy and safety of first-line Rituximab monotherapy for CVID-related GLILD, by assessing symptoms and quality of life alterations, immunological parameters, pulmonary function tests, and lung computed tomography.

View Article and Find Full Text PDF

We report a novel case of SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2) mutation successfully treated with hematopoietic stem cell transplantation. The female patient presented delayed cord separation, chronic diarrhea, skin abscesses, skeletal dysmorphisms, and neutropenia with specific granule deficiency. Analysis of the transcriptomic profile of peripheral blood sorted mature and immature SMARCD2 neutrophils showed defective maturation process that associated with altered expression of genes related to specific, azurophilic, and gelatinase granules, such as LTF, CRISP3, PTX3, and CHI3L1.

View Article and Find Full Text PDF

Objective: Despite the increasing use of rituximab in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), it remains unclear what the optimal dosing is, especially for maintenance of remission. A deeper understanding of post-rituximab B-cell repopulation patterns may aid better-tailored treatment.

Methods: This is a monocentric, retrospective study including ANCA-positive AAV patients receiving a single course of rituximab induction.

View Article and Find Full Text PDF
Article Synopsis
  • MIS-C is a serious condition in children linked to COVID-19 that leads to an overactive immune response.
  • A study analyzed 40 MIS-C patients, finding that they had high inflammatory markers and altered immune cell types during different phases of the disease.
  • Understanding the immune changes in MIS-C could guide better treatments for diseases caused by immune system dysfunction.
View Article and Find Full Text PDF

Dominant negative mutations in CARD11 have been reported in patients with immune dysregulation, severe atopic features, and variable T cell alterations. Data on Natural killer (NK) cells from affected patients are lacking. We report on a 12-year-old boy with severe atopic dermatitis, food induced anaphylaxis and hypogammaglobulinemia harbouring a novel de novo heterozygous variant c.

View Article and Find Full Text PDF

WHIM syndrome is an inherited immune disorder caused by an autosomal dominant heterozygous mutation in CXCR4. The disease is characterized by neutropenia/leukopenia (secondary to retention of mature neutrophils in bone marrow), recurrent bacterial infections, treatment-refractory warts, and hypogammaglobulinemia. All mutations reported in WHIM patients lead to the truncations in the C-terminal domain of CXCR4, R334X being the most frequent.

View Article and Find Full Text PDF

Objectives: Being COVID-19 convalescent plasma (CCP) a therapeutic option that can have a potential impact on the normalization of immunological parameters of COVID-19 affected patients, a detailed analysis of post-infusion immunological changes was conducted in CCP treated patients, aiming to identify possible predictive hallmarks of disease prognosis.

Methods: This prospective observational study describes a cohort of 28 patients who received CCP shortly after being hospitalized for COVID-19 and diagnosed for Acute Respiratory Distress Syndrome. All patients were subjected to a detailed flow cytometry based evaluation of immunological markers at baseline and on days +3 and +7 after transfusion.

View Article and Find Full Text PDF

The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematological diseases. However, approximately 60% of patients relapse after CAR-T cell therapy, and no clear cause for this failure has been identified. The objective of the Bio-CAR-T BS study (ClinicalTrials.

View Article and Find Full Text PDF

CBL syndrome is a Noonan-like RASopathy with heterogeneous clinical phenotype and predisposition to juvenile myelomonocytic leukemia (JMML). Here we describe two patients with identical germline mutation and clinical and immune-hematological overlapping features with autoimmune lymphoproliferative syndrome (ALPS) and B-cell expansion with NF-κB and T-cell anergy (BENTA) syndrome. Increased immature/transitional B cells can be depicted in CBL syndrome, ALPS, and BENTA.

View Article and Find Full Text PDF
Article Synopsis
  • Autoimmunity is prevalent in Common Variable Immune Deficiency (CVID) patients, but the exact mechanisms behind its development remain unclear.
  • Data from a study involving 122 CVID patients distinguished between those with and without autoimmune conditions, revealing that 45.1% showed signs of autoimmunity, with immune thrombocytopenia being the most frequent manifestation.
  • The study found unique immune profiles in patients with autoimmune cytopenias, indicating potential biomarkers or phenotypic features that differentiate them from other CVID patients.
View Article and Find Full Text PDF

The Rubinstein-Taybi syndrome (RSTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, intellectual disability, growth deficiency, and recurrent infections. Mutations in the cyclic adenosine monophosphate response element-binding protein (CREB)-binding protein (CREBBP) or in the E1A-associated protein p300 (EP300) genes have been demonstrated in 55% (RSTS1) and up to 8% of the patients (RSTS2), respectively. Dysfunction of immune response has been reported in a subgroup of individuals with RSTS.

View Article and Find Full Text PDF

Background: Dialysis and kidney transplant patients with moderate-severe COVID-19 have a high mortality rate, around 30%, that is similar in the two populations, despite differences in their baseline characteristics. In these groups, the immunology of the disease has been poorly explored.

Methods: Thirty-two patients on dialysis or with kidney transplant and SARS-CoV-2 infection requiring hospitalization (COV group) were included in our study.

View Article and Find Full Text PDF

Purpose: Jacobsen syndrome (JS) is a rare form of genetic disorder that was recently classified as a syndromic immunodeficiency. Available detailed immunological data from JS patients are limited.

Methods: Clinical and immunological presentation of twelve pediatric patients with JS by means of revision of clinical records, flow cytometry, real-time PCR, and lymphocyte functional testing were collected.

View Article and Find Full Text PDF

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, data registered in the European countries revealed increasing cases of infection in cystic fibrosis (CF) patients. In the course of this pandemic, we enrolled 17 CF patients for a study evaluating inflammatory markers. One of them developed COVID19, giving us the possibility to analyze inflammatory markers in the acute phase as compared to levels detected before and after the infectious episode and to levels measured in the other CF patients enrolled to the study who did not experience COVID-19 and 23 patients referred to our center for SARS-CoV-2 infection.

View Article and Find Full Text PDF

DOCK8 deficiency is a combined immunodeficiency due to biallelic variants in dedicator of cytokinesis 8 () gene. The disease has a wide clinical spectrum encompassing recurrent infections (candidiasis, viral and bacterial infections), virally driven malignancies and immune dysregulatory features, including autoimmune (cytopenia and vasculitis) as well as allergic disorders (eczema, asthma, and food allergy). Hypomorphic function and somatic reversion of has been reported to result in incomplete phenotype without IgE overproduction.

View Article and Find Full Text PDF

Background: SARS-CoV-2 occurs in the majority of children as COVID-19, without symptoms or with a paucisymptomatic respiratory syndrome, but a small proportion of children develop the systemic Multi Inflammatory Syndrome (MIS-C), characterized by persistent fever and systemic hyperinflammation, with some clinical features resembling Kawasaki Disease (KD).

Objective: With this study we aimed to shed new light on the pathogenesis of these two SARS-CoV-2-related clinical manifestations.

Methods: We investigated lymphocyte and dendritic cells subsets, chemokine/cytokine profiles and evaluated the neutrophil activity mediators, myeloperoxidase (MPO), and reactive oxygen species (ROS), in 10 children with COVID-19 and 9 with MIS-C at the time of hospital admission.

View Article and Find Full Text PDF