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Article ; Online: The Immune Response to SARS-CoV-2 Vaccination: Insights Learned From Adult Patients With Common Variable Immune Deficiency.

Quinti, Isabella / Locatelli, Franco / Carsetti, Rita

2022 Volume 12, Page(s) 815404

Abstract: CVID patients have an increased susceptibility to vaccine-preventable infections. The question on the potential benefits of immunization of CVID patients against SARS-CoV-2 offered the possibility to analyze the defective mechanisms of immune responses ... ...

Abstract	CVID patients have an increased susceptibility to vaccine-preventable infections. The question on the potential benefits of immunization of CVID patients against SARS-CoV-2 offered the possibility to analyze the defective mechanisms of immune responses to a novel antigen. In CVID, as in immunocompetent subjects, the role of B and T cells is different between infected and vaccinated individuals. Upon vaccination, variable anti-Spike IgG responses have been found in different CVID cohorts. Immunization with two doses of mRNA vaccine did not generate Spike-specific classical memory B cells (MBCs) but atypical memory B cells (ATM) with low binding capacity to Spike protein. Spike-specific T-cells responses were also induced in CVID patients with a variable frequency, differently from specific T cells produced after multiple exposures to viral antigens following influenza virus immunization and infection. The immune response elicited by SARS-CoV-2 infection was enhanced by subsequent immunization underlying the need to immunize convalescent COVID-19 CVID patients after recovery. In particular, immunization after SARS-Cov-2 infection generated Spike-specific classical memory B cells (MBCs) with low binding capacity to Spike protein and Spike-specific antibodies in a high percentage of CVID patients. The search for a strategy to elicit an adequate immune response post-vaccination in CVID patients is necessary. Since reinfection with SARS-CoV-2 has been documented, at present SARS-CoV-2 positive CVID patients might benefit from new preventing strategy based on administration of anti-SARS-CoV-2 monoclonal antibodies.
MeSH term(s)	Adult ; Antibodies, Monoclonal/immunology ; Antibodies, Viral/immunology ; B-Lymphocyte Subsets/immunology ; COVID-19/complications ; COVID-19/immunology ; COVID-19 Vaccines/immunology ; Common Variable Immunodeficiency/complications ; Common Variable Immunodeficiency/immunology ; Female ; Humans ; Immunogenicity, Vaccine ; Immunologic Memory ; Male ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/immunology ; Vaccination
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Viral ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2022-01-19
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.2021.815404
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Article ; Online: COVID-19 - pathogenesis and immunological findings across the clinical manifestation spectrum.

Carsetti, Rita / Quinti, Isabella / Locatelli, Franco

Current opinion in pulmonary medicine

2021 Volume 27, Issue 3, Page(s) 193–198

Abstract: Purpose of review: The wide spectrum of COVID-19 clinical manifestations demonstrates the determinant role played by the individual immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the course of the disease. Thanks to ... ...

Abstract	Purpose of review: The wide spectrum of COVID-19 clinical manifestations demonstrates the determinant role played by the individual immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the course of the disease. Thanks to the large number of published data, we are beginning to understand the logic of the human response to a virus adapted to bat immunity. Recent findings: Impairment of types I and III interferon responses may facilitate the occurrence of severe COVID-19 with reduced antiviral activity associated to potent inflammation. The human T and B-cell germline repertoire contain the specificities able to react against SARS-CoV-2 antigens. Although inflammation disrupts the structure of germinal centers, memory T and B cells can be found in the blood of patients after mild and severe COVID 19. Summary: Further studies are indispensable to better understand the human immune response to SARS-CoV-2. The diversity of the individual reaction may contribute to explain the clinical manifestation spectrum. Immunological memory can be demonstrated in patients, convalescent from mild, moderate, or severe COVID-19, but we do not know whether asymptomatic individuals have memory of the virus. Tailored vaccination protocols may be needed for individuals with previous SAS-CoV-2 infection.
MeSH term(s)	Asymptomatic Infections ; COVID-19/immunology ; COVID-19/physiopathology ; COVID-19/prevention & control ; COVID-19 Vaccines/pharmacology ; Humans ; Immunity/physiology ; Immunologic Memory ; SARS-CoV-2/immunology ; Severity of Illness Index
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2021-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1285505-4
ISSN	1531-6971 ; 1070-5287 ; 1078-1641
ISSN (online)	1531-6971
ISSN	1070-5287 ; 1078-1641
DOI	10.1097/MCP.0000000000000775
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Article ; Online: Editorial: Challenges in Vaccinology.

Lavelle, Ed C / Carsetti, Rita / Pickl, Winfried F / Wiedermann, Ursula

Frontiers in immunology

2020 Volume 11, Page(s) 632537

MeSH term(s)	COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; Humans ; SARS-CoV-2/immunology ; Vaccinology
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2020-12-17
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.632537
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Article: Immunological characterization of an Italian PANDAS cohort.

Leonardi, Lucia / Lorenzetti, Giulia / Carsetti, Rita / Piano Mortari, Eva / Guido, Cristiana Alessia / Zicari, Anna Maria / Förster-Waldl, Elisabeth / Loffredo, Lorenzo / Duse, Marzia / Spalice, Alberto

Frontiers in pediatrics

2024 Volume 11, Page(s) 1216282

Abstract: This cross-sectional study aimed to contribute to the definition of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) pathophysiology. An extensive immunological assessment has been conducted to investigate ...

Abstract	This cross-sectional study aimed to contribute to the definition of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) pathophysiology. An extensive immunological assessment has been conducted to investigate both immune defects, potentially leading to recurrent Group A β-hemolytic Streptococcus (GABHS) infections, and immune dysregulation responsible for a systemic inflammatory state. Twenty-six PANDAS patients with relapsing-remitting course of disease and 11 controls with recurrent pharyngotonsillitis were enrolled. Each subject underwent a detailed phenotypic and immunological assessment including cytokine profile. A possible correlation of immunological parameters with clinical-anamnestic data was analyzed. No inborn errors of immunity were detected in either group, using first level immunological assessments. However, a trend toward higher TNF-alpha and IL-17 levels, and lower C3 levels, was detected in the PANDAS patients compared to the control group. Maternal autoimmune diseases were described in 53.3% of PANDAS patients and neuropsychiatric symptoms other than OCD and tics were detected in 76.9% patients. ASO titer did not differ significantly between the two groups. A possible correlation between enduring inflammation (elevated serum TNF-α and IL-17) and the persistence of neuropsychiatric symptoms in PANDAS patients beyond infectious episodes needs to be addressed. Further studies with larger cohorts would be pivotal to better define the role of TNF-α and IL-17 in PANDAS pathophysiology.
Language	English
Publishing date	2024-01-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2023.1216282
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Article ; Online: Hyperactivation and altered selection of B cells in patients with paediatric Sjogren's syndrome.

Boni, Alessandra / Nicolai, Rebecca / Caiello, Ivan / Marinaro, Francesca / Farina, Luciapia / Pires Marafon, Denise / Carsetti, Rita / De Benedetti, Fabrizio / Bracaglia, Claudia / Marasco, Emiliano

RMD open

2024 Volume 10, Issue 1

Abstract: Objectives: Paediatric Sjögren's syndrome (pSS) is a rare chronic autoimmune disorder, characterised by inflammation of exocrine glands. B cell hyperactivation plays a central role in adult-onset Sjogren. This study was designed to analyse B cell and T ... ...

Abstract	Objectives: Paediatric Sjögren's syndrome (pSS) is a rare chronic autoimmune disorder, characterised by inflammation of exocrine glands. B cell hyperactivation plays a central role in adult-onset Sjogren. This study was designed to analyse B cell and T cell phenotype, levels of BAFF, and selection of autoreactive B cells in patients with pSS. Methods: A total of 17 patients diagnosed with pSS and 13 healthy donors (controls) comparable for age were enrolled in the study. B cell and T cell subsets and frequency of autoreactive B cells in peripheral blood were analysed by flow cytometry. Levels of BAFF were analysed by ELISA. Results: The relative frequency of total B cells, transitional, naïve and switched memory B cells was similar between pSS patients and controls. In patients with pSS, we observed a reduction in the frequency of unswitched memory B cells, an increased frequency of atypical memory B cells and an expansion of PD1 Conclusions: Our results point to a hyperactivation of B cells in pSS. Current therapies do not seem to affect B cell abnormalities, suggesting that novel therapies targeting specifically B cell hyperactivation need to be implemented for paediatric patients.
MeSH term(s)	Adult ; Humans ; Child ; Sjogren's Syndrome ; B-Lymphocytes ; Autoimmune Diseases ; T-Lymphocyte Subsets
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2023-003800
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Article ; Online: Circulating plasmablasts in children with steroid-sensitive nephrotic syndrome.

Zotta, Federica / Vivarelli, Marina / Carsetti, Rita / Cascioli, Simona / Emma, Francesco / Colucci, Manuela

Pediatric nephrology (Berlin, Germany)

2021 Volume 37, Issue 2, Page(s) 455–459

Abstract: Background: The therapeutic efficacy of B cell-depleting anti-CD20 treatment in both pediatric and adult steroid-sensitive nephrotic syndromes (SSNS) suggests that B cells play a pathogenic role in the disease. In adults with minimal change disease (MCD) ...

Abstract	Background: The therapeutic efficacy of B cell-depleting anti-CD20 treatment in both pediatric and adult steroid-sensitive nephrotic syndromes (SSNS) suggests that B cells play a pathogenic role in the disease. In adults with minimal change disease (MCD), only circulating plasmablasts are increased during the active phase of the disease, among B cell subsets. These cells have not been studied yet in children with SSNS. Methods: We retrospectively quantified by flow cytometry analysis circulating plasmablasts in 107 pediatric patients with SSNS (51 at disease onset, 27 during relapse, and 29 in remission). Data were compared with an equal number of age- and sex-matched healthy donors (HD). Results: Circulating plasmablast levels, expressed as percentage of total CD19 Conclusions: The B cell phenotype of children with SSNS differs from that of adults with MCD. This may justify different therapeutic approaches.
MeSH term(s)	Child ; Female ; Humans ; Male ; Nephrosis, Lipoid/drug therapy ; Nephrotic Syndrome/drug therapy ; Plasma Cells ; Prednisone/therapeutic use ; Retrospective Studies
Chemical Substances	Prednisone (VB0R961HZT)
Language	English
Publishing date	2021-10-18
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-021-05273-8
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Article ; Online: Purification and Characterization of Murine MZ and T2-MZP Cells.

Rosado, M Manuela / Aranburu, Alaitz / Scarsella, Marco / Cascioli, Simona / Giorda, Ezio / Carsetti, Rita

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2270, Page(s) 3–25

Abstract: The spleen is the second major reservoir of B cells in the adult. In the spleen, cells, generated in the bone marrow, are selected, mature, and become part of the peripheral B-cell pool. Murine spleen comprises several B-cell subsets representing various ...

Abstract	The spleen is the second major reservoir of B cells in the adult. In the spleen, cells, generated in the bone marrow, are selected, mature, and become part of the peripheral B-cell pool. Murine spleen comprises several B-cell subsets representing various maturation stages and/or cell functions. The spleen is a complex lymphoid organ organized into two main structures with different functions: the red and white pulp. The red pulp is flowed with blood while the white pulp is organized in primary follicles, with a B-cell area composed of follicular B cells and a T-cell area surrounding a periarterial lymphatic sheath. The frontier between the red and white pulp is defined as the marginal zone (MZ) and contains the MZ B cells. Because B cells, localized in different areas, are characterized by distinct expression levels of B-cell receptor (BCR) and of other surface markers, splenic B-cell subsets can be easily identified and purified by flow cytometry analyses and fluorescence-activated cell sorting (FACS).Here, we will focus on MZ B cells and on their precursors, giving some experimental hints to identify, generate, and isolate these cells. We will combine the use of FACS analysis and confocal microscopy to visualize MZ B cells in cell suspensions and in tissue sections, respectively. We will also give some clues to analyze B-cell repertoire on isolated MZ-B cells.
MeSH term(s)	Animals ; B-Lymphocyte Subsets/metabolism ; B-Lymphocytes/cytology ; Flow Cytometry/methods ; Lymphoid Tissue/immunology ; Mice ; Receptors, Antigen, B-Cell/metabolism ; Spleen/cytology
Chemical Substances	Receptors, Antigen, B-Cell
Language	English
Publishing date	2021-01-19
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1237-8_1
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Article ; Online: IgA Antibodies and IgA Deficiency in SARS-CoV-2 Infection.

Quinti, Isabella / Mortari, Eva Piano / Fernandez Salinas, Ane / Milito, Cinzia / Carsetti, Rita

Frontiers in cellular and infection microbiology

2021 Volume 11, Page(s) 655896

Abstract: A large repertoire of IgA is produced by B lymphocytes with T-independent and T-dependent mechanisms useful in defense against pathogenic microorganisms and to reduce immune activation. IgA is active against several pathogens, including rotavirus, ... ...

Abstract	A large repertoire of IgA is produced by B lymphocytes with T-independent and T-dependent mechanisms useful in defense against pathogenic microorganisms and to reduce immune activation. IgA is active against several pathogens, including rotavirus, poliovirus, influenza virus, and SARS-CoV-2. It protects the epithelial barriers from pathogens and modulates excessive immune responses in inflammatory diseases. An early SARS-CoV-2 specific humoral response is dominated by IgA antibodies responses greatly contributing to virus neutralization. The lack of anti-SARS-Cov-2 IgA and secretory IgA (sIgA) might represent a possible cause of COVID-19 severity, vaccine failure, and possible cause of prolonged viral shedding in patients with Primary Antibody Deficiencies, including patients with Selective IgA Deficiency. Differently from other primary antibody deficiency entities, Selective IgA Deficiency occurs in the vast majority of patients as an asymptomatic condition, and it is often an unrecognized, Studies are needed to clarify the open questions raised by possible consequences of a lack of an IgA response to SARS-CoV-2.
MeSH term(s)	Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; COVID-19/immunology ; Humans ; IgA Deficiency ; Immunoglobulin A/blood ; SARS-CoV-2/immunology ; Virus Shedding
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Immunoglobulin A
Language	English
Publishing date	2021-04-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2021.655896
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Article ; Online: Inflammatory and senescence-associated mediators affect the persistence of humoral response to COVID-19 mRNA vaccination in transfusion-dependent beta-thalassemic patients.

American journal of hematology

2023 Volume 98, Issue 6, Page(s) E145–E147

MeSH term(s)	Humans ; COVID-19/prevention & control ; Blood Transfusion ; beta-Thalassemia/genetics ; beta-Thalassemia/therapy ; RNA, Messenger ; Vaccination ; Antibodies, Viral ; Immunity, Humoral
Chemical Substances	RNA, Messenger ; Antibodies, Viral
Language	English
Publishing date	2023-03-15
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.26905
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Article ; Online: Editorial

Ed C. Lavelle / Rita Carsetti / Winfried F. Pickl / Ursula Wiedermann

Frontiers in Immunology, Vol

Challenges in Vaccinology

2020 Volume 11

Keywords	vaccine ; systems biology ; adjuvant ; emerging infectious diseases ; nosocomial infections ; demographic changes ; Immunologic diseases. Allergy ; RC581-607
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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