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Article ; Online: In adult X-CGD patients, regulatory T cells are expanded while activated T cells display a NOX2-independent ROS increase.

Cammarata, Ilenia / Pinna, Valeria / Pacella, Ilenia / Rotella, Ivano / Soresina, Annarosa / Badolato, Raffaele / Plebani, Alessandro / Pignata, Claudio / Cirillo, Emilia / Zicari, Anna Maria / Violi, Francesco / Carnevale, Roberto / Loffredo, Lorenzo / Piconese, Silvia

Immunology letters

2024 Volume 266, Page(s) 106839

Abstract: The X-linked chronic granulomatous disease (X-CGD), a rare genetic disease characterised by recurrent infections, is caused by mutations of NOX2. Significant proportions of X-CGD patients display signs of immune dysregulation. Regulatory T cells (Tregs) ... ...

Abstract	The X-linked chronic granulomatous disease (X-CGD), a rare genetic disease characterised by recurrent infections, is caused by mutations of NOX2. Significant proportions of X-CGD patients display signs of immune dysregulation. Regulatory T cells (Tregs) are CD4
MeSH term(s)	Adult ; Humans ; Granulomatous Disease, Chronic/genetics ; Granulomatous Disease, Chronic/metabolism ; T-Lymphocytes, Regulatory ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; Reactive Oxygen Species/metabolism ; Mutation
Chemical Substances	NADPH Oxidases (EC 1.6.3.-) ; Reactive Oxygen Species
Language	English
Publishing date	2024-02-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	445150-8
ISSN	1879-0542 ; 0165-2478
ISSN (online)	1879-0542
ISSN	0165-2478
DOI	10.1016/j.imlet.2024.106839
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Article ; Online: Omenn Syndrome due to RAG1 Mutation Presenting With Nonimmune Hydrops Fetalis in Two Siblings.

Valeri, Lara / Lugli, Licia / Iughetti, Lorenzo / Soresina, Annarosa / Giliani, Silvia / Porta, Fulvio / Berardi, Alberto

Pediatrics

2022 Volume 149, Issue 1

Abstract: Omenn syndrome (OS) is a rare variant of severe combined immunodeficiency characterized by susceptibility to severe opportunistic infections and peculiar manifestations, such as protein-losing erythroderma, alopecia, hepatosplenomegaly, lymphadenopathies, ...

Abstract	Omenn syndrome (OS) is a rare variant of severe combined immunodeficiency characterized by susceptibility to severe opportunistic infections and peculiar manifestations, such as protein-losing erythroderma, alopecia, hepatosplenomegaly, lymphadenopathies, and severe diarrhea. The typical form of the disease is caused by hypomorphic mutation of the recombination-activating genes (RAG1 and RAG2), which are critical in initiating the molecular processes leading to lymphocyte and immunoglobulin receptor formation. Affected patients lack B cells, whereas autoreactive oligoclonal T cells infiltrate the skin, gut, spleen, and liver. In the absence of hematopoietic stem cell transplantation, patients with OS usually succumb early in life because of opportunistic infections. The incidence of OS is estimated to be <1 per 1 000 000; however, the actual frequency is difficult to ascertain. We report 2 siblings affected by OS due to a homozygous frameshift mutation (NM_000448.3:c.519delT, p.E174Sfs*26) in the RAG1 gene presenting with nonimmune hydrops fetalis (NIHF). To the best of our knowledge, this is the first reported association between OS and NIHF. NIHF specifically refers to the presence of ≥2 abnormal fluid collections in the fetus, without red blood cell alloimmunization. A broad spectrum of pathologies is associated with NIHF; however, in ∼20% of the cases, the primary cause remains unclear. Understanding the etiology of NIHF is essential for guiding clinical management, determining prognosis, and informing parents regarding recurrence risk. Our case contributes to expanding the spectrum of OS presentation and highlights the importance of a complete immunologic and genetic workup in otherwise unexplained cases of NIHF.
MeSH term(s)	Alopecia/complications ; Dermatitis, Exfoliative/complications ; Frameshift Mutation ; Homeodomain Proteins/genetics ; Homozygote ; Humans ; Hydrops Fetalis/etiology ; Infant, Newborn ; Male ; Morocco ; Pedigree ; Severe Combined Immunodeficiency/complications ; Severe Combined Immunodeficiency/diagnosis ; Severe Combined Immunodeficiency/genetics ; Siblings
Chemical Substances	Homeodomain Proteins ; RAG-1 protein (128559-51-3)
Language	English
Publishing date	2022-01-17
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	207677-9
ISSN	1098-4275 ; 0031-4005
ISSN (online)	1098-4275
ISSN	0031-4005
DOI	10.1542/peds.2021-052411
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Article: Vasculitis and vasculopathy associated with inborn errors of immunity: an overview.

Federici, Silvia / Cinicola, Bianca Laura / La Torre, Francesco / Castagnoli, Riccardo / Lougaris, Vassilios / Giardino, Giuliana / Volpi, Stefano / Caorsi, Roberta / Leonardi, Lucia / Corrente, Stefania / Soresina, Annarosa / Cancrini, Caterina / Insalaco, Antonella / Gattorno, Marco / De Benedetti, Fabrizio / Marseglia, Gian Luigi / Del Giudice, Michele Miraglia / Cardinale, Fabio

Frontiers in pediatrics

2024 Volume 11, Page(s) 1258301

Abstract: Systemic autoinflammatory diseases (SAIDs) are disorders of innate immunity, which are characterized by unprovoked recurrent flares of systemic inflammation often characterized by fever associated with clinical manifestations mainly involving the ... ...

Abstract	Systemic autoinflammatory diseases (SAIDs) are disorders of innate immunity, which are characterized by unprovoked recurrent flares of systemic inflammation often characterized by fever associated with clinical manifestations mainly involving the musculoskeletal, mucocutaneous, gastrointestinal, and nervous systems. Several conditions also present with varied, sometimes prominent, involvement of the vascular system, with features of vasculitis characterized by variable target vessel involvement and organ damage. Here, we report a systematic review of vasculitis and vasculopathy associated with inborn errors of immunity.
Language	English
Publishing date	2024-01-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2023.1258301
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Article ; Online: Patients with STAT1 Gain-of-function Mutations Display Increased Apoptosis which is Reversed by the JAK Inhibitor Ruxolitinib.

Dotta, Laura / Todaro, Francesca / Baronio, Manuela / Giacomelli, Mauro / Pinelli, Marinella / Giambarda, Martina / Brognoli, Beatrice / Greco, Silvia / Rota, Francesca / Cortesi, Manuela / Soresina, Annarosa / Moratto, Daniele / Tomasi, Cesare / Ferraro, Rosalba Monica / Giliani, Silvia / Badolato, Raffaele

Journal of clinical immunology

2024 Volume 44, Issue 4, Page(s) 85

Abstract: Introduction: The signal transducer and activator of transcription (STAT1) gain-of-function (GOF) syndrome accounts for most cases of chronic mucocutaneous candidiasis but is characterized by a broader clinical phenotype that may include bacterial, ... ...

Abstract	Introduction: The signal transducer and activator of transcription (STAT1) gain-of-function (GOF) syndrome accounts for most cases of chronic mucocutaneous candidiasis but is characterized by a broader clinical phenotype that may include bacterial, viral, or invasive fungal infections, autoimmunity, autoinflammatory manifestations, vascular complications, or malignancies. The severity of lymphopenia may vary and influence the infectious morbidity. Methods: In our cohort of seven STAT1-GOF patients, we investigated the mechanisms that may determine T lymphopenia, we characterized the interferon gene signature (IGS) and analyzed the effect of ruxolitinib in reverting the immune dysregulation. Results: STAT1-GOF patients exhibited increased T lymphocyte apoptosis that was significantly augmented in both resting conditions and following stimulation with mitogens and IFNα, as evaluated by flow cytometry by Annexin V/ Propidium iodide assay. The JAK inhibitor ruxolitinib significantly reduced the IFNα-induced hyperphosphorylation of STAT1 and reverted the stimulation-induced T-cell apoptosis, in vitro. In two adult STAT1-GOF patients, the JAKinib treatment ameliorated chronic mucocutaneous candidiasis and lymphopenia. Most STAT1-GOF patients, particularly those who had autoimmunity, presented increased IGS that significantly decreased in the two patients during ruxolitinib treatment. Conclusion: In STAT1-GOF patients, T lymphocyte apoptosis is increased, and T lymphopenia may determine higher risk of severe infections. The JAKinib target therapy should be evaluated to treat severe chronic candidiasis and lymphopenia, and to downregulate the IFNs in patients with autoinflammatory or autoimmune manifestations.
MeSH term(s)	Adult ; Humans ; Gain of Function Mutation ; Janus Kinase Inhibitors/therapeutic use ; Candidiasis, Chronic Mucocutaneous/drug therapy ; Candidiasis, Chronic Mucocutaneous/genetics ; Interferons ; Lymphopenia ; STAT1 Transcription Factor/metabolism ; Thrombocytopenia ; Nitriles ; Pyrazoles ; Pyrimidines
Chemical Substances	ruxolitinib (82S8X8XX8H) ; Janus Kinase Inhibitors ; Interferons (9008-11-1) ; STAT1 Transcription Factor ; STAT1 protein, human ; Nitriles ; Pyrazoles ; Pyrimidines
Language	English
Publishing date	2024-04-05
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-024-01684-y
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Article ; Online: COVID-19 Pneumonia with Migratory Pattern in Agammaglobulinemic Patients: A Report of Two Cases and Review of Literature.

Degli Antoni, Melania / Crosato, Verena / Pennati, Francesca / Borghesi, Andrea / Cristini, Graziella / Allegri, Roberto / Capone, Susanna / Bergamasco, Alberto / Soresina, Annarosa / Badolato, Raffaele / Maroldi, Roberto / Quiros-Roldan, Eugenia / Matteelli, Alberto / Castelli, Francesco / Focà, Emanuele

Tomography (Ann Arbor, Mich.)

2023 Volume 9, Issue 3, Page(s) 894–900

Abstract: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in serum immunoglobulins and early-onset infections. Coronavirus Disease-2019 (COVID-19) pneumonia in immunocompromised patients presents clinical and ... ...

Abstract	X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in serum immunoglobulins and early-onset infections. Coronavirus Disease-2019 (COVID-19) pneumonia in immunocompromised patients presents clinical and radiological peculiarities which have not yet been completely understood. Very few cases of agammaglobulinemic patients with COVID-19 have been reported since the beginning of the pandemic in February 2020. We report two cases of migrant COVID-19 pneumonia in XLA patients.
MeSH term(s)	Humans ; COVID-19/complications ; Pneumonia ; Genetic Diseases, X-Linked ; Agammaglobulinemia/complications ; Agammaglobulinemia/diagnostic imaging
Language	English
Publishing date	2023-04-23
Publishing country	Switzerland
Document type	Review ; Case Reports
ISSN	2379-139X
ISSN (online)	2379-139X
DOI	10.3390/tomography9030073
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Article ; Online: Pathogenesis of Autoimmune Cytopenias in Inborn Errors of Immunity Revealing Novel Therapeutic Targets.

Cortesi, Manuela / Soresina, Annarosa / Dotta, Laura / Gorio, Chiara / Cattalini, Marco / Lougaris, Vassilios / Porta, Fulvio / Badolato, Raffaele

Frontiers in immunology

2022 Volume 13, Page(s) 846660

Abstract: Autoimmune diseases are usually associated with environmental triggers and genetic predisposition. However, a few number of autoimmune diseases has a monogenic cause, mostly in children. These diseases may be the expression, isolated or associated with ... ...

Abstract	Autoimmune diseases are usually associated with environmental triggers and genetic predisposition. However, a few number of autoimmune diseases has a monogenic cause, mostly in children. These diseases may be the expression, isolated or associated with other symptoms, of an underlying inborn error of immunity (IEI). Autoimmune cytopenias (AICs), including immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), autoimmune neutropenia (AN), and Evans' syndrome (ES) are common presentations of immunological diseases in the pediatric age, with at least 65% of cases of ES genetically determined. Autoimmune cytopenias in IEI have often a more severe, chronic, and relapsing course. Treatment refractoriness also characterizes autoimmune cytopenia with a monogenic cause, such as IEI. The mechanisms underlying autoimmune cytopenias in IEI include cellular or humoral autoimmunity, immune dysregulation in cases of hemophagocytosis or lymphoproliferation with or without splenic sequestration, bone marrow failure, myelodysplasia, or secondary myelosuppression. Genetic characterization of autoimmune cytopenias is of fundamental importance as an early diagnosis improves the outcome and allows the setting up of a targeted therapy, such as CTLA-4 IgG fusion protein (Abatacept), small molecule inhibitors (JAK-inhibitors), or gene therapy. Currently, gene therapy represents one of the most attractive targeted therapeutic approaches to treat selected inborn errors of immunity. Even in the absence of specific targeted therapies, however, whole exome genetic testing (WES) for children with chronic multilineage cytopenias should be considered as an early diagnostic tool for disease diagnosis and genetic counseling.
MeSH term(s)	Anemia, Hemolytic, Autoimmune/diagnosis ; Anemia, Hemolytic, Autoimmune/genetics ; Anemia, Hemolytic, Autoimmune/therapy ; Autoimmunity/genetics ; Child ; Humans ; Purpura, Thrombocytopenic, Idiopathic/diagnosis ; Purpura, Thrombocytopenic, Idiopathic/genetics ; Purpura, Thrombocytopenic, Idiopathic/therapy ; Thrombocytopenia/complications
Language	English
Publishing date	2022-04-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.846660
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Article ; Online: Immune tolerance breakdown in inborn errors of immunity: Paving the way to novel therapeutic approaches.

Giardino, Giuliana / Romano, Roberta / Lougaris, Vassilios / Castagnoli, Riccardo / Cillo, Francesca / Leonardi, Lucia / La Torre, Francesco / Soresina, Annarosa / Federici, Silvia / Cancrini, Caterina / Pacillo, Lucia / Toriello, Elisabetta / Cinicola, Bianca Laura / Corrente, Stefania / Volpi, Stefano / Marseglia, Gian Luigi / Pignata, Claudio / Cardinale, Fabio

Clinical immunology (Orlando, Fla.)

2023 Volume 251, Page(s) 109302

Abstract: Up to 25% of the patients with inborn errors of immunity (IEI) also exhibit immunodysregulatory features. The association of immune dysregulation and immunodeficiency may be explained by different mechanisms. The understanding of mechanisms underlying ... ...

Abstract	Up to 25% of the patients with inborn errors of immunity (IEI) also exhibit immunodysregulatory features. The association of immune dysregulation and immunodeficiency may be explained by different mechanisms. The understanding of mechanisms underlying immune dysregulation in IEI has paved the way for the development of targeted treatments. In this review article, we will summarize the mechanisms of immune tolerance breakdown and the targeted therapeutic approaches to immune dysregulation in IEI.
MeSH term(s)	Humans ; Immune Tolerance ; Immune System Diseases/genetics ; Immune System Diseases/therapy
Language	English
Publishing date	2023-03-24
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2023.109302
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Article ; Online: When a Nontuberculous Mycobacterial Infection Reveals an Error of Immunity: A Single Center's Experience.

Morreale, Alessia / Dotta, Laura / Vairo, Donatella / Bazzana, Tullia / Lougaris, Vassilios / Soresina, Annarosa / Plebani, Alessandro / Giliani, Silvia Clara / Porta, Fulvio / Matteelli, Alberto / Redaelli De Zinis, Luca Oscar / Badolato, Raffaele

The Pediatric infectious disease journal

2022 Volume 41, Issue 5, Page(s) 427–429

Abstract: We present an algorithm that may be applied in case of a diagnosis of pediatric nontuberculous mycobacterial disease to identify the patients who may require an immunologic assessment to discover a possible underlying immune system defect predisposing to ...

Abstract	We present an algorithm that may be applied in case of a diagnosis of pediatric nontuberculous mycobacterial disease to identify the patients who may require an immunologic assessment to discover a possible underlying immune system defect predisposing to their nontuberculous mycobacterial infections.
MeSH term(s)	Child ; Humans ; Mycobacterium Infections, Nontuberculous/diagnosis ; Mycobacterium Infections, Nontuberculous/microbiology ; Nontuberculous Mycobacteria
Language	English
Publishing date	2022-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392481-6
ISSN	1532-0987 ; 0891-3668
ISSN (online)	1532-0987
ISSN	0891-3668
DOI	10.1097/INF.0000000000003461
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Article ; Online: COVID-19 Pneumonia with Migratory Pattern in Agammaglobulinemic Patients

Melania Degli Antoni / Verena Crosato / Francesca Pennati / Andrea Borghesi / Graziella Cristini / Roberto Allegri / Susanna Capone / Alberto Bergamasco / Annarosa Soresina / Raffaele Badolato / Roberto Maroldi / Eugenia Quiros-Roldan / Alberto Matteelli / Francesco Castelli / Emanuele Focà

Tomography, Vol 9, Iss 73, Pp 894-

A Report of Two Cases and Review of Literature

2023 Volume 900

Abstract	X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in serum immunoglobulins and early-onset infections. Coronavirus Disease-2019 (COVID-19) pneumonia in immunocompromised patients presents clinical and radiological peculiarities which have not yet been completely understood. Very few cases of agammaglobulinemic patients with COVID-19 have been reported since the beginning of the pandemic in February 2020. We report two cases of migrant COVID-19 pneumonia in XLA patients.
Keywords	COVID-19 ; X-linked agammaglobulinemia ; migrant pneumonia ; organizing pneumonia ; computed tomography ; Computer applications to medicine. Medical informatics ; R858-859.7
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Primary atopic disorders and chronic skin disease.

Cinicola, Bianca Laura / Corrente, Stefania / Castagnoli, Riccardo / Lougaris, Vassilios / Giardino, Giuliana / Leonardi, Lucia / Volpi, Stefano / La Torre, Francesco / Federici, Silvia / Soresina, Annarosa / Cancrini, Caterina / Marseglia, Gian Luigi / Cardinale, Fabio

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology

2022 Volume 33 Suppl 27, Page(s) 65–68

Abstract: Primary atopic disorders (PADs) are monogenic diseases characterized by allergy or atopy-related symptoms as fundamental features. In patients with PADs, primary immune deficiency and immune dysregulation symptoms are usually coexist. Chronic skin ... ...

Abstract	Primary atopic disorders (PADs) are monogenic diseases characterized by allergy or atopy-related symptoms as fundamental features. In patients with PADs, primary immune deficiency and immune dysregulation symptoms are usually coexist. Chronic skin disease, manifesting with erythroderma, severe atopic dermatitis or eczema, and urticaria, is one of the main features observed in PADs, such as hyper-IgE syndromes, Omenn syndrome, Wiskott-Aldrich syndrome, IPEX-linked syndrome, skin barrier disorders, as well as some autoinflammatory diseases. The recognition of PADs in the context of an allergic phenotype is crucial to ensure prompt diagnosis and appropriate treatment. This article provides an overview of the main PADs with skin involvement.
MeSH term(s)	Eczema ; Humans ; Hypersensitivity, Immediate ; Job Syndrome/genetics ; Skin Diseases ; Urticaria/diagnosis
Language	English
Publishing date	2022-02-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1057059-7
ISSN	1399-3038 ; 0905-6157 ; 0906-5784
ISSN (online)	1399-3038
ISSN	0905-6157 ; 0906-5784
DOI	10.1111/pai.13633
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