Alberto Tommasini

IRCCS Ospedale Infantile Burlo Garofolo | Ospedale Burlo · Laboratories of Immunopathology

Juvenile recurrent parotitis is an uncommon condition characterised by recurrent episodes of parotid swelling that affects school-aged and pre-school children and shows a typical tendency to self-resolution during adolescence. To date, etiopathogenetic hypotheses and treatment options are still debated, as there are no current guidelines for its di...

Up to 70% of patients with Wiskott-Aldrich Syndrome (WAS) develop autoimmune and inflammatory manifestations. Dysregulation of interleukin (IL)-1 may be involved in their pathogenesis, yet there is little evidence on treatment with anti-IL-1 agents in these patients. We conducted a multicenter retrospective analysis of nine patients with WAS treate...

Objectives Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) are poorly informative about interferon (IFN)‐related disorders. In these conditions, the measure of the interferon score (IS), obtained by measuring the expression of IFN‐stimulated genes, has been proposed. Flow cytometry‐based assays measuri...

Activated phosphoinositide 3-kinase (PI3Kδ) Syndrome (APDS) is an inborn error of immunity (IEI) with a variable clinical presentation, characterized by infection susceptibility and immune dysregulation that may overlaps with other Primary Immune Regulatory Disorders (PIRDs). The rarity of the disease, its recent discovery, and the multiform /multi...

Inborn errors of immunity are a rapidly-developing area of clinical study. Based on the description of a small set of disorders with a significant risk of infection that may be identified with a small number of lab tests, the definition has been expanded to include a broader range of diseases that may necessitate a more intricate diagnostic process...

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34⁺ cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and e...

The pathogenic role of the overactivated ABL1 tyrosine kinase (TK) pathway is well recognized in some forms of BCR-ABL1 like acute lymphoblastic leukemia (ALL); TK inhibitors represent a useful therapeutic choice in these patients who respond poorly to conventional chemotherapy. Here we report a novel peptide biosensor (PABL)-ELISA assay to investi...

Background:The definition of psoriatic arthritis in pediatrics (JPsA) is controversial. The study purpose to describe clinical and laboratory characteristics and responses to therapies in children with psoriatic arthropathies. Methods: A retrospective multicentre observational study enrolling subjects meeting the ILAR criteria for juvenile psoriati...

Background H Syndrome is a rare genetic condition caused by biallelic pathogenic variants in the SLC29A3 gene. It is characterized by a wide range of clinical manifestations, many of which are related to the immune-rheumatological field. These include scleroderma-like skin changes, deforming arthritis, and enlarged lymph nodes. The condition also f...

Background Erythropoietic protoporphyria is a rare disorder which represents an important health problem in children, causing painful photosensitivity. Little is known on the correlation between genetic profile and clinical manifestations. The standard of care for Erythropoietic protoporphyria is based on avoiding sun and using sun protections, but...

We report the first known case of PAMI syndrome associated with pulmonary arterial hypertension (PAH) with a positive response to cyclophosphamide and pulmonary vasodilators. The patient's history began at 7 months with severe pancytopenia and fever. As time progressed, migrating arthritis, hepatosplenomegaly, and a growth deficit manifested withou...

Background Tocilizumab is a humanized monoclonal antibody that acts as an IL-6 receptor antagonist. Intravenous tocilizumab is considered an option for children with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis. In contrast, the potential of subcutaneous drug use with this indication is more controversial. Due to the decreas...

Periodic fever is not uncommon in childhood and is often ascribed to autoinflammatory conditions; however, it may be present also in children with cancer. We here describe the case of a 3-year-old boy with acute lymphoblastic leukemia who initially presented with a 4-month history of recurrent, stereotyped episodes of fever and localized joint pain...

Background: Juvenile idiopathic arthritis can be refractory to some or all treatment regimens, therefore new medications are needed to treat this population. This trial assessed the efficacy and safety of baricitinib, an oral Janus kinase 1/2-selective inhibitor, versus placebo in patients with juvenile idiopathic arthritis. Methods: This phase...

Primary complement system (C) deficiencies are rare but notably associated with an increased risk of infections, autoimmunity, or immune disorders. Patients with terminal pathway C-deficiency have a 1,000- to 10,000-fold-higher risk of Neisseria meningitidis infections and should be therefore promptly identified to minimize the likelihood of furthe...

Objectives: The interferon score (IS) quantifies the expression of interferon-stimulated genes in peripheral blood, providing an indirect estimate of interferon-mediated inflammation in rheumatological disorders. This study explores the clinical significance of IS among a cohort of patients affected by juvenile idiopathic arthritis (JIA) and its r...

Inborn errors of immunity (IEI) associated with immune dysregulation are not sufficiently addressed in shared recommendation, resulting in delayed diagnosis and high morbidity. The availability of precision medicine for some of these immune defects makes it urgent to evaluate effective strategies to diagnose and treat such defects before the occurr...

Background COPA syndrome is a rare hereditary inflammatory disease caused by mutations in the gene encoding the coatomer protein subunit alpha, causing excessive production of type I interferon. This case is a reminder for the general paediatrician, highlighting the relevance of the association between arthritis and lung involvement in toddlers. C...

Behçet’s disease (BD) is a rare chronic inflammatory condition associated with variable-vessel vasculitis, systemic involvement and relapsing course. It is characterized by a wide clinical heterogeneity, presenting with mucocutaneous, ocular, articular, gastrointestinal, neurological and vascular manifestations in the long term, with a high risk of...

Background: The role of musculoskeletal ultrasound in JIA is still controversial, although there is growing evidence on its utility, especially in the diagnosis of tenosynovitis. Methods: We presented a retrospective cross-sectional study of a group of patients with JIA with ankle swelling followed in a Pediatric Rheumatology Service of a tertia...

In the last two decades two new paradigms changed our way of perceiving primary immunodeficiencies: An increasing number of immune defects are more associated with inflammatory or autoimmune features rather than with infections. Some primary immune defects are due to hyperactive pathways that can be targeted by specific inhibitors, providing innova...

Data on the effective burden of the SARS-CoV-2 pandemic in the pediatric population are limited. We aimed at assessing the prevalence of SARS-CoV-2 IgG antibodies in children at three subsequent time-points. The study was conducted between January 2021 and July 2021 among children referring to the Research Institute for Maternal and Child Health “B...

La fascia di età 5-11 anni non farà in tempo a vaccinarsi tutta per assicurarsi un diritto scolastico che non può e non deve vivere una sorta di ricatto vaccinale. Ma la scelta dei genitori dovrà tenere conto (e molto) anche della libertà sociale ed educativa dei propri figli. E, come abbiamo piu’ volte detto, “la corsa a vaccinarsi”, per la salute...

Background: The T-cell engager antibody blinatumomab (BlincytoT⁢M) represents a promising rescue therapy for relapsed/refractory CD19+ acute lymphoblastic leukemia (B-ALL), although ~20-30% of patients still do not respond to treatment. Blinatumomab creates a tight synapsis between CD3+ T-lymphocytes and leukemic CD19+ B-cells, resulting in a gran...

Background Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders that comprise Crohn’s disease (CD) and ulcerative colitis (UC). Recent discoveries have brought much attention to the genetic predisposition of patients with IBD. Here we evaluate the interaction between IBD genetic risk factors susceptibility and CD occurrence in a...

The pathogenic role of the overactivated ABL1 tyrosine kinase (TK) pathway is well recognized in some forms of BCR-ABL1 like acute lymphoblastic leukemia (ALL); TK inhibitors represent a useful therapeutic choice in these patients who respond poorly to conventional chemotherapy. Here we report a novel peptide biosensor (PABL)-ELISA assay to investi...

Mevalonate Kinase Deficiency (MKD) is a rare inborn disease belonging to the family of periodic fever syndromes. The MKD phenotype is characterized by systemic inflammation involving multiple organs, including the nervous system. Current anti-inflammatory approaches to MKD are only partially effective and do not act specifically on neural inflammat...

Type I interferonopathies are autoinflammatory monogenic disorders arising from excessive production of interferons. Some manifestations like chilblains, neurologic involvement, arthritis and lipodystrophy may be shared by several diseases. Measure of interferon score and genetic analysis can assist a definite diagnosis. Among immunomodulant drugs,...

Activated PI3K-kinase Delta Syndrome (APDS) is an autosomal-dominant primary immunodeficiency (PID) caused by the constitutive activation of the PI3Kδ kinase. The consequent hyperactivation of the PI3K-Akt-mTOR pathway leads to an impaired T- and B-cells differentiation and function, causing progressive lymphopenia, hypogammaglobulinemia and hyper...

RASopathies and mTORopathies are groups of genetic syndromes associated with increased activation of the RAS-MAPK or the PI3K-AKT-mTOR pathway, resulting in altered cell proliferation during embryonic and postnatal development. The RAS-MAPK and the PI3K-AKT-mTOR pathways are connected to each other and play a crucial role in adaptive immunity. Howe...

We are very grateful to the authors for the contents reported in their viewpoint raising doubts about the significance of long-covid in pediatric and adolescent age (1). The two recent works concerning the possible existence of a long-covid syndrome in pediatric age report simply aspects that may have to deal with emotional disturbances. Similarly...

Common variable immunodeficiency disorders (CVID) are a group of rare diseases of the immune system and the most common symptomatic primary antibody deficiency in adults. The “variable” aspect of CVID refers to the approximately half of the patients who develop non-infective complications, mainly autoimmune features, in particular organ specific au...

Background Juvenile idiopathic inflammatory myopathies (JIIMs) are a group of heterogenous, acquired, autoimmune disorders that affect the muscle. While the association between IIMs and malignancy has been widely reported in adults, cancer-associated myositis (CAM) is rare in children, so that routine malignancy screening is not generally performed...

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), a cruciferous-derived bioactive molecule, in...

Background Tenosynovitis can occur in patients with Juvenile Idiopathic Arthritis (JIA) and may be clinically difficult to distinguish from joint synovitis. The role of musculoskeletal ultrasound (msk-US) is still discussed in the management of JIA but recent studies supported the utility of msk-US especially in detection of tenosynovitis. There is...

More and more findings suggest that neurological disorders could have an immunopathological cause. Thus, immune-targeted therapies are increasingly proposed in neurology (even if often controversial), as anakinra, inhibiting IL-1 for febrile inflammatory illnesses, and JAK inhibitors for anti-interferons treatment. Precision medicine in neurology c...

Background Recurrent aphthous stomatitis with systemic signs of inflammation can be encountered in inflammatory bowel disease, Behçet’s disease (BD), Systemic Lupus Erythematosus (SLE). In addition, it has been proposed that cases with very early onset in childhood can be underpinned by rare monogenic defects of immunity, which may require targeted...

Background: We describe the case of an 11-year-old boy affected by chronic granulomatous disease complicated by a Crohn's like colitis needing prolonged treatment with oral corticosteroids. Case presentation: His therapy for the control of severe oral mucositis was based on topical clobetasol, which did not decrease once the steroids were discon...

Cytoplasmic nucleic acids sensing through cGAS-STING-TBK1 pathway is crucial for the production of antiviral interferons (IFNs). IFN production can also be induced by lipopolysaccharide (LPS) stimulation through Toll-like receptor 4 (TLR4) in appropriate conditions. Of note, both IFN production and dysregulated LPS-response could play a role in the...

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...

X-linked Chronic Granulomatous Disease (CGD) is a rare inherited immunodeficiency characterized by early life-threatening infections from bacteria and fungi in male children. Female carriers of X-linked CGD usually do not develop any manifestations of the disease, yet in rare cases they may present with CGD-related manifestations due to skewed X ch...

There is growing literature about the SARS-CoV-2 pathogenetic effects exerted during pregnancy and whether vertical transmission or premature birth is possible. It is not well known whether changes in the immune system of pregnant women may lead to a marked susceptibility to infectious processes and the risk of adverse maternal and neonatal complic...

Primary immunodeficiencies (PIDs) are a large and growing group of disorders commonly associated with recurrent infections. However, nowadays, we know that PIDs often carry with them consequences related to organ or hematologic autoimmunity, autoinflammation, and lymphoproliferation in addition to simple susceptibility to pathogens. Alongside this...

Primary immunodeficiency (PID) with immune dysregulation may present with early onset gastrointestinal autoimmune disorders. When gastrointestinal autoimmunity is associated with multiple extraintestinal immune system dysfunction the diagnosis of PID is straightforward. However, with the advent of next generation sequencing technologies, genetic de...

During COVID-19 outbreak, a large number of children with severe inflammatory disease has been reported. This condition, named Pediatric Multi-inflammatory Syndrome temporally associated with COVID-19 (PIMS-TS) or Multisystem Inflammatory Syndrome associated with Coronavirus Disease 2019 (MIS-C), shares some clinical features with Kawasaki disease...

Background - Eosinophilic granulomatosis with polyangiitis, formerly known as Churg-Strauss syndrome, is an extremely rare systemic vasculitis in the paediatric population. The hallmarks of eosinophilic granulomatosis with polyangiitis are a long history of asthma and peripheral eosinophilia with eosinophilic inflammation that may involve several o...

Off-label use of medications is still a common practice in pediatric rheumatology. JAK inhibitors are authorized in adults in the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Although their use is not authorized yet in children, JAK inhibitors, based on their mechanism of action and on clinical experiences in small...

Primary immunodeficiencies (PIDs) are heterogeneous disorders, characterized by variable clinical and immunological features. National PID registries offer useful insights on the epidemiology, diagnosis, and natural history of these disorders. In 1999, the Italian network for primary immunodeficiencies (IPINet) was established. We report on data co...

Medical advances have dramatically improved the long-term prognosis of children and adolescents with Inborn Errors of Immunity (IEIs). Transfer of medical care of individuals with pediatric IEIs to adult facilities is a complex task also for the high number of distinct disorders, that requires involvement of patients and both pediatric and adult ca...

Background: FBLIM1 gene has been recently demonstrated to be involved in the pathogenesis of bone sterile inflammation. The aim of the study is to evaluate the prevalence of FBLIM1 gene variants in a cohort of 80 Italian patients with Chronic Non-bacterial Osteomyelitis (CNO). Methods: The coding regions of FBLIM1 gene were sequenced in a cohort...

As the outbreak of the new coronavirus (SARS-CoV-2) infection is spreading globally, great effort is being made to understand the disease pathogenesis and host factors that predispose to disease progression in an attempt to find a window of opportunity for intervention. In addition to the direct cytopathic effect of the virus, the host hyper-inflam...