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Article ; Online: HBV messing with the B-cell genome leads to DLBCL.

Visentini, Marcella / Casato, Milvia

2018 Volume 131, Issue 24, Page(s) 2602–2603

MeSH term(s)	Adult ; B-Lymphocytes ; Child ; Hepatitis B virus ; Humans ; Lymphoma, Large B-Cell, Diffuse
Language	English
Publishing date	2018-06-13
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2018-05-847525
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Article ; Online: Persistence of Pathogenic B-Cell Clones and Relapse of Cryoglobulinemic Vasculitis in HCV-Cured Patients.

Visentini, Marcella / Fiorilli, Massimo / Casato, Milvia

Gastroenterology

2018 Volume 156, Issue 1, Page(s) 291

MeSH term(s)	B-Lymphocytes ; Cryoglobulinemia ; Hepatitis C, Chronic ; Humans ; Recurrence ; Vasculitis
Language	English
Publishing date	2018-10-10
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2018.06.094
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Article: Opposite Effects of mRNA-Based and Adenovirus-Vectored SARS-CoV-2 Vaccines on Regulatory T Cells: A Pilot Study.

La Gualana, Francesca / Maiorca, Francesca / Marrapodi, Ramona / Villani, Francesca / Miglionico, Marzia / Santini, Stefano Angelo / Pulcinelli, Fabio / Gragnani, Laura / Piconese, Silvia / Fiorilli, Massimo / Basili, Stefania / Casato, Milvia / Stefanini, Lucia / Visentini, Marcella

Biomedicines

2023 Volume 11, Issue 2

Abstract: New-generation mRNA and adenovirus vectored vaccines against SARS-CoV-2 spike protein are endowed with immunogenic, inflammatory and immunomodulatory properties. Recently, BioNTech developed a noninflammatory tolerogenic mRNA vaccine (MOGm1Ψ) that ... ...

Abstract	New-generation mRNA and adenovirus vectored vaccines against SARS-CoV-2 spike protein are endowed with immunogenic, inflammatory and immunomodulatory properties. Recently, BioNTech developed a noninflammatory tolerogenic mRNA vaccine (MOGm1Ψ) that induces in mice robust expansion of antigen-specific regulatory T (Treg) cells. The Pfizer/BioNTech BNT162b2 mRNA vaccine against SARS-CoV-2 is identical to MOGm1Ψ except for the lipid carrier, which differs for containing lipid nanoparticles rather than lipoplex. Here we report that vaccination with BNT162b2 led to an increase in the frequency and absolute count of CD4
Language	English
Publishing date	2023-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11020511
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Article ; Online: From the pathogenesis to the cure of indolent B-cell lymphoproliferative disorders associated with hepatitis C virus infection: which role for direct-acting antivirals?

Visentini, Marcella / Fiorilli, Massimo / Casato, Milvia

Expert review of hematology

2017 Volume 10, Issue 8, Page(s) 719–727

Abstract: Introduction: Hepatitis C virus (HCV) causes monoclonal B cell lymphoproliferative disorders ranging from benign, such as in mixed cryoglobulinemia (MC), to indolent or aggressive lymphomas. MC and indolent lymphomas commonly regress when HCV is ... ...

Abstract	Introduction: Hepatitis C virus (HCV) causes monoclonal B cell lymphoproliferative disorders ranging from benign, such as in mixed cryoglobulinemia (MC), to indolent or aggressive lymphomas. MC and indolent lymphomas commonly regress when HCV is eradicated with interferon (IFN) therapy; however, sustained virologic response (SVR) to IFN is achieved only in ~50% of patients. The new all oral direct-acting antivirals (DAA), yielding nearly 100% SVR, promise a breakthrough in the treatment of HCV-associated lymphoproliferative disorders, but experience is still scanty. Areas covered: A literature search was performed to summarize current pathogenetic hypotheses in HCV-associated indolent lymphoproliferative disorders and to identify clinical trials focused on the use of antiviral therapy. Hematological outcomes of IFN-based and IFN-free DAA-based regimens were compared. Expert commentary: While MC appears to regress in most patients after DAA therapy, the still very limited experience with indolent lymphomas suggests that hematologic responses might be less than those observed with IFN. Furthermore, anecdotal observations of early progression to aggressive lymphoma after DAA are disquieting. Large studies are needed to determine the values and limits of DAA for treating HCV-associated indolent lymphomas and to identify subgroups at risk of non-response.
MeSH term(s)	Antiviral Agents/therapeutic use ; B-Lymphocytes/metabolism ; B-Lymphocytes/pathology ; B-Lymphocytes/virology ; Clonal Evolution ; Drug Therapy, Combination ; Hepacivirus ; Hepatitis C/complications ; Hepatitis C/drug therapy ; Hepatitis C/virology ; Humans ; Interferons/therapeutic use ; Lymphoproliferative Disorders/diagnosis ; Lymphoproliferative Disorders/etiology ; Lymphoproliferative Disorders/therapy ; Treatment Outcome
Chemical Substances	Antiviral Agents ; Interferons (9008-11-1)
Language	English
Publishing date	2017-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2516804-6
ISSN	1747-4094 ; 1747-4086
ISSN (online)	1747-4094
ISSN	1747-4086
DOI	10.1080/17474086.2017.1349607
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Article ; Online: Persistence of monoclonal B-cell expansion and intraclonal diversification despite virus eradication in patients affected by hepatitis C virus-associated lymphoproliferative disorders.

Mazzaro, Cesare / Visentini, Marcella / Gragnani, Laura / Vit, Filippo / Tissino, Erika / Pozzo, Federico / Papotti, Robel / Casato, Milvia / Zignego, Anna Linda / Bittolo, Tamara / Zucchetto, Antonella / Degan, Massimo / Bomben, Riccardo / Gattei, Valter

British journal of haematology

2023 Volume 203, Issue 2, Page(s) 237–243

Abstract: We investigated 23 hepatitis C virus (HCV)-infected patients with overt lymphoproliferative diseases (15 cases) or monoclonal B lymphocytosis (8 cases) treated with direct agent antiviral (DAAs) per clinical practice. DAA therapy yielded undetectable HCV- ...

Abstract	We investigated 23 hepatitis C virus (HCV)-infected patients with overt lymphoproliferative diseases (15 cases) or monoclonal B lymphocytosis (8 cases) treated with direct agent antiviral (DAAs) per clinical practice. DAA therapy yielded undetectable HCV-RNA, the complete response of cryoglobulinemia vasculitis and related signs, whilst the presence of B-cell clones (evaluated by flow cytometry, IGHV, and BCL2-IGH rearrangements), detected in 19/23 cases at baseline, was maintained (17/19). Similarly, IGHV intraclonal diversification, supporting an antigen-driven selection mechanism, was identified in B-cell clones at baseline and end of follow-up. DAA therapy alone, despite HCV eradication and good immunological responses, was less effective on the pathological B-cell clones.
Language	English
Publishing date	2023-07-25
Publishing country	England
Document type	Journal Article
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.19002
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Article ; Online: CD21

Visentini, Marcella / Pellicano, Chiara / Leodori, Giorgia / Marrapodi, Ramona / Colantuono, Stefania / Gigante, Antonietta / Casato, Milvia / Rosato, Edoardo

Clinical and experimental immunology

2021 Volume 205, Issue 2, Page(s) 128–134

Abstract: The objective of this study was to evaluate the predictive role of ... ...

Abstract	The objective of this study was to evaluate the predictive role of CD21
MeSH term(s)	B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Biomarkers/metabolism ; Female ; Humans ; Male ; Middle Aged ; Receptors, Complement 3d/metabolism ; Scleroderma, Systemic/immunology ; Scleroderma, Systemic/metabolism ; Skin Ulcer/immunology ; Skin Ulcer/metabolism
Chemical Substances	Biomarkers ; Receptors, Complement 3d
Language	English
Publishing date	2021-06-06
Publishing country	England
Document type	Journal Article
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1111/cei.13604
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Article: High prevalence of gluten sensitivity in a cohort of patients with undifferentiated connective tissue disease.

Conti, V / Leone, M C / Casato, M / Nicoli, M / Granata, G / Carlesimo, M

European annals of allergy and clinical immunology

2015 Volume 47, Issue 2, Page(s) 54–57

Abstract: Objectives: The aim of this study was to investigate if co-morbid conditions as hepatitis C virus infection and celiac disease may be associated to undifferentiated connective tissue disease.: Methods: We studied retrospectively and prospectively 52 ... ...

Abstract	Objectives: The aim of this study was to investigate if co-morbid conditions as hepatitis C virus infection and celiac disease may be associated to undifferentiated connective tissue disease. Methods: We studied retrospectively and prospectively 52 patients with diagnosis of undifferentiated connective tissue disease, subdivided, according to Vaz criteria, in systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome-like subgroups. Serological markers of celiac disease as anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies were investigated. An esophagogastroduodenoscopy with duodenal biopsy and histological examination was proposed to patients with positive celiac disease serology. In addition antibodies directed to hepatitis C virus and total IgA-antibodies were investigated. Results: Six patients (11,5%) were positive for celiac disease serological tests although two of them were asymptomatic. Four patients underwent an esophagogastroduodenoscopy, showing total or subtotal villous atrophy at duodenal biopsies. Hepatitis C virus serology was negative in all patients and none had IgA deficiency. 83% of celiac patients showed a scleroderma-like phenotype. We observed a statistically higher incidence of autoimmune symptoms in patients with gluten sensitivity. Fatigue and myalgia regressed early after the beginning of gluten-free diet. Conclusions: In our cohort of patients the prevalence of celiac disease was higher than that reported in the general population. We believe that all patients with diagnosis of undifferentiated connective tissue disease, especially those with a systemic sclerosis-like presentation, should be investigated for celiac disease, even in absence of gastrointestinal symptoms. Gluten-free diet should be early recommended to all patients having undifferentiated connective tissue disease and gluten sensitivity.
MeSH term(s)	Adult ; Aged ; Autoantibodies/blood ; Biomarkers/blood ; Biopsy ; Celiac Disease/blood ; Celiac Disease/diagnosis ; Celiac Disease/diet therapy ; Celiac Disease/epidemiology ; Celiac Disease/immunology ; Comorbidity ; Connective Tissue Diseases/blood ; Connective Tissue Diseases/diagnosis ; Connective Tissue Diseases/epidemiology ; Connective Tissue Diseases/immunology ; Diet, Gluten-Free ; Duodenum/pathology ; Endoscopy, Gastrointestinal ; Female ; Hepatitis C/epidemiology ; Humans ; Lupus Erythematosus, Systemic/epidemiology ; Male ; Middle Aged ; Predictive Value of Tests ; Prevalence ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Rome/epidemiology ; Scleroderma, Systemic/epidemiology ; Serologic Tests ; Sjogren's Syndrome/epidemiology ; Young Adult
Chemical Substances	Autoantibodies ; Biomarkers
Language	English
Publishing date	2015-03
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2105540-3
ISSN	1764-1489 ; 0397-9148
ISSN	1764-1489 ; 0397-9148
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Article ; Online: Dual stimulation by autoantigen and CpG fosters the proliferation of exhausted rheumatoid factor-specific CD21

Del Padre, Martina / Marrapodi, Ramona / Minafò, Ylenia A / Piano Mortari, Eva / Radicchio, Giovanna / Bocci, Chiara / Gragnani, Laura / Camponeschi, Alessandro / Colantuono, Stefania / Stefanini, Lucia / Basili, Stefania / Carsetti, Rita / Fiorilli, Massimo / Casato, Milvia / Visentini, Marcella

Frontiers in immunology

2023 Volume 14, Page(s) 1094871

Abstract: Introduction: Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of B cells expressing B cell receptors (BCRs), often encoded by the VH1-69 variable gene, endowed with both rheumatoid factor (RF) and anti-HCV ... ...

Abstract	Introduction: Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of B cells expressing B cell receptors (BCRs), often encoded by the VH1-69 variable gene, endowed with both rheumatoid factor (RF) and anti-HCV specificity. These cells display an atypical CD21low phenotype and functional exhaustion evidenced by unresponsiveness to BCR and Toll-like receptor 9 (TLR9) stimuli. Although antiviral therapy is effective on MC vasculitis, pathogenic B cell clones persist long thereafter and can cause virus-independent disease relapses. Methods: Clonal B cells from patients with HCV-associated type 2 MC or healthy donors were stimulated with CpG or heath-aggregated IgG (as surrogate immune complexes) alone or in combination; proliferation and differentiation were then evaluated by flow cytometry. Phosphorylation of AKT and of the p65 NF-kB subunit were measured by flow cytometry. TLR9 was quantified by qPCR and by intracellular flow cytometry, and MyD88 isoforms were analyzed using RT-PCR. Discussion: We found that dual triggering with autoantigen and CpG restored the capacity of exhausted VH1-69pos B cells to proliferate. The signaling mechanism for this BCR/TLR9 crosstalk remains elusive, since TLR9 mRNA and protein as well as MyD88 mRNA were normally expressed and CpG-induced phosphorylation of p65 NF-kB was intact in MC clonal B cells, whereas BCR-induced p65 NF-kB phosphorylation was impaired and PI3K/Akt signaling was intact. Our findings indicate that autoantigen and CpG of microbial or cellular origin may unite to foster persistence of pathogenic RF B cells in HCV-cured MC patients. BCR/TLR9 crosstalk might represent a more general mechanism enhancing systemic autoimmunity by the rescue of exhausted autoreactive CD21low B cells.
MeSH term(s)	Humans ; Autoantigens ; Cell Proliferation ; Cryoglobulinemia/etiology ; Hepacivirus ; Hepatitis C ; Myeloid Differentiation Factor 88/metabolism ; NF-kappa B/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rheumatoid Factor ; Toll-Like Receptor 9/metabolism ; CpG Islands ; Receptors, Complement 3d/immunology ; B-Lymphocytes/immunology
Chemical Substances	Autoantigens ; Myeloid Differentiation Factor 88 ; NF-kappa B ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Rheumatoid Factor (9009-79-4) ; Toll-Like Receptor 9 ; Receptors, Complement 3d
Language	English
Publishing date	2023-02-08
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.2023.1094871
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Article ; Online: High prevalence of past hepatitis B virus infection in diffuse large B cell lymphoma: a retrospective study from Italy.

Visentini, Marcella / Pica, Andrea / D'Ippolito, Giancarlo / Sculco, Eleonora / La Gualana, Francesca / Gragnani, Laura / Miglionico, Marzia / Mazzaro, Cesare / Fiorilli, Massimo / Basili, Stefania / Martelli, Maurizio / Di Rocco, Alice / Casato, Milvia / Gentile, Giuseppe / Pulsoni, Alessandro

Annals of hematology

2023 Volume 102, Issue 12, Page(s) 3457–3463

Abstract: Studies from high endemic areas, mostly China, indicate that surface antigen positive ( ... ...

Abstract	Studies from high endemic areas, mostly China, indicate that surface antigen positive (HBsAg
MeSH term(s)	Humans ; Male ; Female ; Hepatitis B virus/metabolism ; Retrospective Studies ; Hepatitis B Surface Antigens ; Hepatitis B, Chronic/complications ; Hepatitis B, Chronic/epidemiology ; Prevalence ; Hepatitis B/epidemiology ; Hepatitis B/complications ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Hepatitis B Antibodies
Chemical Substances	Hepatitis B Surface Antigens ; Hepatitis B Antibodies
Language	English
Publishing date	2023-08-31
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1064950-5
ISSN	1432-0584 ; 0939-5555 ; 0945-8077
ISSN (online)	1432-0584
ISSN	0939-5555 ; 0945-8077
DOI	10.1007/s00277-023-05412-1
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Article ; Online: Reply.

Zignego, Anna Linda / Gragnani, Laura / Visentini, Marcella / Casato, Milvia

Hepatology (Baltimore, Md.)

2017 Volume 65, Issue 5, Page(s) 1771–1772

Language	English
Publishing date	2017-05
Publishing country	United States
Document type	Letter
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.28977
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