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  1. AU="Tessarin, Giulio"
  2. AU="Sato, Tsutomu"
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  1. Article ; Online: Monogenic forms of common variable immunodeficiency and implications on target therapeutic approaches.

    Tessarin, Giulio / Baronio, Manuela / Lougaris, Vassilios

    Current opinion in allergy and clinical immunology

    2023  Volume 23, Issue 6, Page(s) 461–466

    Abstract: Purpose of review: Common variable immunodeficiency (CVID) is the most common symptomatic inborn error of immunity. The disorder is characterized by variable clinical and immunological manifestations, and, in a small minority of patients, a monogenic ... ...

    Abstract Purpose of review: Common variable immunodeficiency (CVID) is the most common symptomatic inborn error of immunity. The disorder is characterized by variable clinical and immunological manifestations, and, in a small minority of patients, a monogenic cause may be identified. In this review, we focalized on three different monogenic forms of CVID-like disease.
    Recent findings: Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare disorder characterized by hyperactivated class I phosphatidylinositol-3 kinase (PI3K) pathway. Affected patients present with respiratory infectious episodes, impaired viral clearance and lymphoproliferation. Recently, a direct PI3K inhibitor has been approved and it showed encouraging results both in controlling clinical and immunological manifestations of the disease. On the other hand, patients with defects in CTLA-4 or LRBA gene present with life-threatening immune dysregulation, autoimmunity and lymphocytic infiltration of multiple organs. Abatacept, a soluble cytotoxic T lymphocyte antigen 4 (CTLA-4) fusion protein that acts as a costimulation modulator, has been widely implemented for affected patients with good results as bridge treatment.
    Summary: Understanding the biological basis of CVID is important not only for enriching our knowledge of the human immune system, but also for setting the basis for potential targeted treatments in this disorder.
    MeSH term(s) Humans ; CTLA-4 Antigen/genetics ; CTLA-4 Antigen/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Common Variable Immunodeficiency/genetics ; Common Variable Immunodeficiency/therapy ; Autoimmunity ; Adaptor Proteins, Signal Transducing/metabolism
    Chemical Substances CTLA-4 Antigen ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; LRBA protein, human (EC 2.7.10.-) ; Adaptor Proteins, Signal Transducing
    Language English
    Publishing date 2023-09-28
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 2088710-3
    ISSN 1473-6322 ; 1528-4050
    ISSN (online) 1473-6322
    ISSN 1528-4050
    DOI 10.1097/ACI.0000000000000947
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Lymphocyte alterations in patients with Common Variable Immunodeficiency (CVID) and autoimmune manifestations.

    Rossi, Stefano / Baronio, Manuela / Gazzurelli, Luisa / Tessarin, Giulio / Baresi, Giulia / Chiarini, Marco / Moratto, Daniele / Badolato, Raffaele / Plebani, Alessandro / Lougaris, Vassilios

    Clinical immunology (Orlando, Fla.)

    2022  Volume 241, Page(s) 109077

    Abstract: Introduction: Autoimmunity is a common feature in CVID patients. To date the mechanisms leading to the development of such complications are not fully elucidated.: Materials and methods: Data from 122 CVID patients subdivided in three groups based on ...

    Abstract Introduction: Autoimmunity is a common feature in CVID patients. To date the mechanisms leading to the development of such complications are not fully elucidated.
    Materials and methods: Data from 122 CVID patients subdivided in three groups based on the absence of autoimmunity (n-AI) or the presence of hematologic autoimmune phenomena (Cy-AI) or non-hematologic autoimmune phenomena (n-Cy-AI) were evaluated.
    Results: We identified a total of 128 autoimmune manifestations in 55/122 patients (45.1%). 30/122 (24.6%) patients presented hematologic autoimmune phenomena while 29/122 (23.8%) presented gastrointestinal autoimmune involvement. Immune thrombocytopenia was the most common manifestation (27/122; 22.1%), followed by autoimmune hemolytic anemia (18/122; 14.8%) and autoimmune enteropathy (17/122; 13.9%). Cy-AI patients displayed higher CD4
    Conclusions: CVID patients developing autoimmune cytopenias display characteristic immune phenotypic features.
    MeSH term(s) Autoimmunity ; CD4-Positive T-Lymphocytes ; Common Variable Immunodeficiency ; Humans ; Immunophenotyping ; Purpura, Thrombocytopenic, Idiopathic
    Language English
    Publishing date 2022-07-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2022.109077
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  3. Article ; Online: CARD11 dominant negative mutation leads to altered human Natural Killer cell homeostasis.

    Baronio, Manuela / Gazzurelli, Luisa / Rezzola, Sara / Rossi, Stefano / Tessarin, Giulio / Marinoni, Maddalena / Salpietro, Annamaria / Fiore, Michele / Moratto, Daniele / Chiarini, Marco / Badolato, Raffaele / Parolini, Silvia / Tabellini, Giovanna / Lougaris, Vassilios

    Immunobiology

    2023  Volume 228, Issue 3, Page(s) 152381

    Abstract: 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 ... ...

    Abstract 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.169G > A; p.Glu57Lys in CARD11. The dominant negative effect of this mutation was confirmed on both CD4
    MeSH term(s) Male ; Humans ; Child ; Killer Cells, Natural ; T-Lymphocytes ; Mutation ; Homeostasis ; Guanylate Cyclase/genetics ; Guanylate Cyclase/metabolism ; CARD Signaling Adaptor Proteins/genetics
    Chemical Substances CARD11 protein, human (EC 4.6.1.2) ; Guanylate Cyclase (EC 4.6.1.2) ; CARD Signaling Adaptor Proteins
    Language English
    Publishing date 2023-04-05
    Publishing country Netherlands
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 563292-4
    ISSN 1878-3279 ; 0171-2985
    ISSN (online) 1878-3279
    ISSN 0171-2985
    DOI 10.1016/j.imbio.2023.152381
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  4. Article ; Online: Rituximab Monotherapy Is Effective as First-Line Treatment for Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in CVID Patients.

    Tessarin, Giulio / Baronio, Manuela / Gazzurelli, Luisa / Rossi, Stefano / Chiarini, Marco / Moratto, Daniele / Giliani, Silvia Clara / Bondioni, Maria Pia / Badolato, Raffaele / Lougaris, Vassilios

    Journal of clinical immunology

    2023  Volume 43, Issue 8, Page(s) 2091–2103

    Abstract: 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 ... ...

    Abstract 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.All six GLILD patients received Rituximab infusions as a first-line treatment. Rituximab was administered at 375 mg/m
    MeSH term(s) Humans ; Rituximab/therapeutic use ; Common Variable Immunodeficiency/complications ; Common Variable Immunodeficiency/diagnosis ; Common Variable Immunodeficiency/drug therapy ; Lung Diseases, Interstitial/diagnosis ; Lung Diseases, Interstitial/drug therapy ; Lung Diseases, Interstitial/etiology ; Quality of Life ; Lung
    Chemical Substances Rituximab (4F4X42SYQ6)
    Language English
    Publishing date 2023-09-27
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 779361-3
    ISSN 1573-2592 ; 0271-9142
    ISSN (online) 1573-2592
    ISSN 0271-9142
    DOI 10.1007/s10875-023-01587-4
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  5. Article ; Online: Clinical and immunological analysis of a large kindred affected by autoimmune lymphoproliferative syndrome (ALPS) due to a novel TNFRSF6 mutation displaying age dependent disease activity.

    Tessarin, Giulio / Baronio, Manuela / Gazzurelli, Luisa / Rossi, Stefano / Gorio, Chiara / Bertoni, Elisa / Chiarini, Marco / Moratto, Daniele / Mazza, Cinzia / Porta, Fulvio / Badolato, Raffalele / Lougaris, Vassilios

    Clinical immunology (Orlando, Fla.)

    2022  Volume 245, Page(s) 109136

    MeSH term(s) Humans ; Autoimmune Lymphoproliferative Syndrome/genetics ; fas Receptor/genetics ; Mutation ; Autoimmune Diseases ; Lymphoproliferative Disorders
    Chemical Substances fas Receptor
    Language English
    Publishing date 2022-09-30
    Publishing country United States
    Document type Letter
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2022.109136
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  6. Article ; Online: Complete CD95/FAS deficiency due to complex homozygous germline TNFRSF6 mutations in an adult patient with mild autoimmune lymphoproliferative syndrome (ALPS).

    Tessarin, Giulio / Mazza, Cinzia / Baronio, Manuela / Gazzurelli, Luisa / Rossi, Stefano / Moratto, Daniele / Badolato, Raffaele / Rensing-Ehl, Anne / Ehl, Stephan / Warnatz, Klaus / Rosanelli, Carlo / Morello, Enrico / Plebani, Alessandro / Lougaris, Vassilios

    Clinical immunology (Orlando, Fla.)

    2021  Volume 228, Page(s) 108757

    MeSH term(s) Autoimmune Lymphoproliferative Syndrome/diagnosis ; Autoimmune Lymphoproliferative Syndrome/etiology ; Autoimmune Lymphoproliferative Syndrome/metabolism ; Autoimmune Lymphoproliferative Syndrome/therapy ; Biomarkers ; Disease Susceptibility ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Hematopoietic Stem Cell Transplantation ; High-Throughput Nucleotide Sequencing ; Homozygote ; Humans ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; fas Receptor/deficiency
    Chemical Substances Biomarkers ; FAS protein, human ; fas Receptor
    Language English
    Publishing date 2021-05-13
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2021.108757
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  7. Article ; Online: First-ever convulsive seizures in children presenting to the emergency department: risk factors for seizure recurrence and diagnosis of epilepsy.

    Sartori, Stefano / Nosadini, Margherita / Tessarin, Giulio / Boniver, Clementina / Frigo, Anna Chiara / Toldo, Irene / Bressan, Silvia / Da Dalt, Liviana

    Developmental medicine and child neurology

    2018  Volume 61, Issue 1, Page(s) 82–90

    Abstract: Aim: Aetiologies of first-ever convulsive seizures may be diverse, not all leading to recurrence or epilepsy diagnosis. We aimed to describe the epidemiology of first-ever convulsive seizures in children, investigating risk factors for recurrence and ... ...

    Abstract Aim: Aetiologies of first-ever convulsive seizures may be diverse, not all leading to recurrence or epilepsy diagnosis. We aimed to describe the epidemiology of first-ever convulsive seizures in children, investigating risk factors for recurrence and epilepsy diagnosis.
    Method: This was a retrospective study of children presenting with a first-ever convulsive seizure to a tertiary-care paediatric emergency department (PED) in Italy, in a 12-month period (2011-2012).
    Results: One hundred and eight children (57 males, 51 females) presented to the PED for a first-ever convulsive seizure; 90.7% were 6 months to 6 years old (median age 1y 10mo, mean 2y 7mo, range 0mo-14y 4mo). Seizure duration was less than 5 minutes in 76.8%. Seizures were 'unprovoked' in 19.4% and 'provoked' in 80.6%. At 4-year follow-up, 37.9% of patients experienced recurrence and 13.6% received a diagnosis of epilepsy. Factors significantly associated with recurrence were the 'unprovoked' nature of the first seizure, multiple seizures in the first 24 hours, positive family history of febrile seizures or epilepsy, and pre-existing neurological conditions/problems. Factors significantly associated with a diagnosis of epilepsy were the 'unprovoked' nature of the first seizure, age older than 6 years, pre-existing neurological conditions/problems, and focal onset of first seizure.
    Interpretation: Children presenting to the PED with first-ever convulsive seizures represent a heterogeneous group. The identification of prognostic factors for recurrence and epilepsy diagnosis may help provide tailored counselling and follow-up.
    What this paper adds: Seizures were 'unprovoked' in 19.4% and 'provoked' in 80.6% of children presenting to the emergency department. At 4-year follow-up, 37.9% relapsed, and 13.6% received a diagnosis of epilepsy. 'Unprovoked' first seizure, family history of febrile seizures, and pre-existing neurological conditions were associated with recurrence. 'Unprovoked' first seizure, age younger than 6 years, and pre-existing neurological conditions were associated with epilepsy diagnosis.
    MeSH term(s) Child ; Child, Preschool ; Emergency Service, Hospital ; Epilepsy/diagnosis ; Epilepsy/epidemiology ; Epilepsy/therapy ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Recurrence ; Retrospective Studies ; Risk Factors ; Seizures/diagnosis ; Seizures/epidemiology ; Seizures/therapy
    Language English
    Publishing date 2018-09-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 80369-8
    ISSN 1469-8749 ; 0012-1622
    ISSN (online) 1469-8749
    ISSN 0012-1622
    DOI 10.1111/dmcn.14015
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  8. Article ; Online: Paediatric MAS/HLH caused by a novel monoallelic activating mutation in p110δ.

    Lougaris, Vassilios / Baronio, Manuela / Castagna, Andrea / Tessarin, Giulio / Rossi, Stefano / Gazzurelli, Luisa / Benvenuto, Alessio / Moratto, Daniele / Chiarini, Marcho / Cattalini, Marco / Facchetti, Mattia / Palumbo, Laura / Giliani, Silvia / Girelli, Maria Federica / Badolato, Raffaele / Bondioni, Maria Pia / Facchetti, Fabio / Meini, Antonella / Plebani, Alessandro

    Clinical immunology (Orlando, Fla.)

    2020  Volume 219, Page(s) 108543

    Abstract: This study provides evidence for the first time for APDS-1 presenting as MAS/HLH, with evident clinical implications in patient's management and prognosis. ...

    Abstract This study provides evidence for the first time for APDS-1 presenting as MAS/HLH, with evident clinical implications in patient's management and prognosis.
    MeSH term(s) Child ; Class I Phosphatidylinositol 3-Kinases/genetics ; Humans ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Lymphohistiocytosis, Hemophagocytic/genetics ; Macrophage Activation Syndrome/diagnosis ; Macrophage Activation Syndrome/genetics ; Male ; Mutation ; Primary Immunodeficiency Diseases/diagnosis ; Primary Immunodeficiency Diseases/genetics
    Chemical Substances Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; PIK3CD protein, human (EC 2.7.1.137)
    Language English
    Publishing date 2020-07-16
    Publishing country United States
    Document type Case Reports ; Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2020.108543
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  9. Article ; Online: Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in Common Variable Immunodeficiency (CVID): A Multicenter Retrospective Study of Patients From Italian PID Referral Centers.

    Cinetto, Francesco / Scarpa, Riccardo / Carrabba, Maria / Firinu, Davide / Lougaris, Vassilios / Buso, Helena / Garzi, Giulia / Gianese, Sabrina / Soccodato, Valentina / Punziano, Alessandra / Lagnese, Gianluca / Tessarin, Giulio / Costanzo, Giulia / Landini, Nicholas / Vio, Stefania / Bondioni, Maria Pia / Consonni, Dario / Marasco, Carolina / Del Giacco, Stefano /
    Rattazzi, Marcello / Vacca, Angelo / Plebani, Alessandro / Fabio, Giovanna / Spadaro, Giuseppe / Agostini, Carlo / Quinti, Isabella / Milito, Cinzia

    Frontiers in immunology

    2021  Volume 12, Page(s) 627423

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2021-03-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.627423
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  10. Article: Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients.

    Tessarin, Giulio / Rossi, Stefano / Baronio, Manuela / Gazzurelli, Luisa / Colpani, Michael / Benvenuto, Alessio / Zunica, Fiammetta / Cardinale, Fabio / Martire, Baldassarre / Brescia, Letizia / Costagliola, Giorgio / Luti, Laura / Casazza, Gabriella / Menconi, Maria Cristina / Saettini, Francesco / Palumbo, Laura / Girelli, Maria Federica / Badolato, Raffaele / Lanzi, Gaetana /
    Chiarini, Marco / Moratto, Daniele / Meini, Antonella / Giliani, Silvia / Bondioni, Maria Pia / Plebani, Alessandro / Lougaris, Vassilios

    Journal of clinical medicine

    2020  Volume 9, Issue 10

    Abstract: Activated phosphoinositide 3-kinase delta syndrome 1 (APDS-1) is a recently described inborn error of immunity caused by monoallelic gain-of-function mutations in ... ...

    Abstract Activated phosphoinositide 3-kinase delta syndrome 1 (APDS-1) is a recently described inborn error of immunity caused by monoallelic gain-of-function mutations in the
    Language English
    Publishing date 2020-10-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm9103335
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