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  1. Article ; Online: Evaluation of autoantibody profile in healthy subjects after mRNA vaccination against COVID-19.

    Fiorelli, Denise / Caruso, Vincenza / Belardi, Riccardo / Bernardini, Sergio / Nuccetelli, Marzia

    International immunopharmacology

    2023  Volume 122, Page(s) 110592

    Abstract: Background: SARS-CoV-2 severe acute respiratory syndrome has rapidly spread worldwide since 2019. All scientific and technological forces have concentrated towards the formulation of vaccines to contain the disease. In less than one year (December 2020) ...

    Abstract Background: SARS-CoV-2 severe acute respiratory syndrome has rapidly spread worldwide since 2019. All scientific and technological forces have concentrated towards the formulation of vaccines to contain the disease. In less than one year (December 2020) a first messenger RNA vaccine (Comirnaty, BioNTech/Pfizer) was authorized. However, the research community has wondered about possible side effects on the immune system, given the vaccines administration in phase 4.
    Aim: This study aims to evaluate the mRNA vaccine impact on the development of possible positive autoantibody profile in healthcare workers without any previous underlying pathology, after first, second and booster dose of Pfizer vaccine, by determining: circulating immune complexes concentrations (CIC); anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3) autoantibodies, the presence of antinuclear antibodies (ANA) and subsequent second level tests (extractable nuclear antigen (ENA) screen, double-strand DNA, extractable nuclear antigen (ANA) profile).
    Methods: The subjects were divided according to anti-SARS-CoV-2 IgG RBD antibodies increasing concentrations in: Group I < 10 BAU/ml (N = 114); Group II > 1000 BAU/ml (N = 112); Group III > 2500 BAU/ml (N = 78).
    Results: Our data show no autoreactive response changes over time in healthy subjects after vaccination. In fact, evaluation of ANA, CIC, anti-MPO, anti-PR3 and the detection of specific autoantigens, did not display significant variations.
    Conclusions: The results suggest the exclusion of a correlation between the administration of the vaccine and the possible onset of autoimmune disorders. Nevertheless, further investigations will be needed to test for any long-term side effects on an ever-growing population.
    MeSH term(s) Humans ; Autoantibodies ; COVID-19/prevention & control ; Healthy Volunteers ; SARS-CoV-2 ; Vaccination ; Antibodies, Antinuclear ; Antibodies, Viral ; Antigens, Nuclear
    Chemical Substances Autoantibodies ; Antibodies, Antinuclear ; Antibodies, Viral ; Antigens, Nuclear
    Language English
    Publishing date 2023-07-03
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2043785-7
    ISSN 1878-1705 ; 1567-5769
    ISSN (online) 1878-1705
    ISSN 1567-5769
    DOI 10.1016/j.intimp.2023.110592
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    Zs.A 5408: Show issues Location:
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  2. Article ; Online: Autoantibody profiles assessment in individuals with persistent olfactory impairment following SARS-CoV-2 infection.

    Fiorelli, Denise / Francavilla, Beatrice / Velletrani, Gianluca / Maurantonio, Sara / Passali, Francesco Maria / Bernardini, Sergio / Di Girolamo, Stefano / Nuccetelli, Marzia

    International immunopharmacology

    2024  Volume 129, Page(s) 111599

    Abstract: Background: Olfactory impairment, particularly hyposmia and anosmia, has emerged as a distinctive early symptom of SARS-CoV-2. Drawing on the historical association of autoimmune diseases with olfactory function, this study delves into the connections ... ...

    Abstract Background: Olfactory impairment, particularly hyposmia and anosmia, has emerged as a distinctive early symptom of SARS-CoV-2. Drawing on the historical association of autoimmune diseases with olfactory function, this study delves into the connections between COVID-19, autoimmunity, and persistent olfactory dysfunctions, focusing on individuals experiencing long-lasting smell disorders (3-18 months post-SARS-CoV-2 infection).
    Methods: The study comprised 36 Long Covid patients with persistent olfactory dysfunctions, alongside two control groups. Olfactory functionality was assessed using the Sniffin' Sticks extended test. Non-invasive olfactory mucosa brushing and nasal secretions were processed for nasal samples, while serum samples were obtained through peripheral venous sampling. A panel of autoantibodies, including Immunocirculating Complexes, ANA, ENA, and AECA, was investigated in serum and brush supernatant samples.
    Results: Contrary to expectations, the absence of traditional autoantibodies challenges the proposed autoimmune etiology of Long Covid-associated olfactory dysfunction. However, the presence and potential pathogenic role of AECA suggest viral cytopathic and inflammatory involvement in specific anatomical districts. One hypothesis explores the impact of inflammation and cytokine release induced by the viral infection, altering neuronal signaling and contributing to persistent hyposmia.
    Conclusion: This research contributes to our understanding of the complex relationships between autoimmunity, olfactory impairment, and COVID-19. The absence of classical autoantibodies challenges prevailing theories, while the prominence of AECA hints at unique viral-induced pathogenic mechanisms. By unraveling these complexities, this study enhances our comprehension of post-acute sequelae, offering valuable perspectives on immune-mediated responses in the aftermath of the pandemic.
    MeSH term(s) Humans ; COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Anosmia ; Autoantibodies ; Olfaction Disorders/etiology ; Autoimmune Diseases
    Chemical Substances Autoantibodies
    Language English
    Publishing date 2024-02-07
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2043785-7
    ISSN 1878-1705 ; 1567-5769
    ISSN (online) 1878-1705
    ISSN 1567-5769
    DOI 10.1016/j.intimp.2024.111599
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  3. Article ; Online: Constitutive NOS Production Is Modulated by Alzheimer's Disease Pathology Depending on APOE Genotype.

    Bonomi, Chiara Giuseppina / Martorana, Alessandro / Fiorelli, Denise / Nuccetelli, Marzia / Placidi, Fabio / Mercuri, Nicola Biagio / Motta, Caterina

    International journal of molecular sciences

    2024  Volume 25, Issue 7

    Abstract: Both the endothelial (eNOS) and the neuronal (nNOS) isoforms of constitutive Nitric Oxide Synthase have been implicated in vascular dysfunctions in Alzheimer's disease (AD). We aimed to explore the relationship between amyloid pathology and NO dynamics ... ...

    Abstract Both the endothelial (eNOS) and the neuronal (nNOS) isoforms of constitutive Nitric Oxide Synthase have been implicated in vascular dysfunctions in Alzheimer's disease (AD). We aimed to explore the relationship between amyloid pathology and NO dynamics by comparing the cerebrospinal fluid (CSF) levels of nNOS and eNOS of 8 healthy controls (HC) and 27 patients with a clinical diagnosis of Alzheimer's disease and isolated CSF amyloid changes, stratified according to APOE ε genotype (APOE ε3 = 13, APOE ε4 = 14). Moreover, we explored the associations between NOS isoforms, CSF AD biomarkers, age, sex, cognitive decline, and blood-brain barrier permeability. In our cohort, both eNOS and nNOS levels were increased in APOE ε3 with respect to HC and APOE ε4. CSF eNOS inversely correlated with CSF Amyloid-β42 selectively in carriers of APOE ε3; CSF nNOS was negatively associated with age and CSF p-tau only in the APOE ε4 subgroup. Increased eNOS could represent compensative vasodilation to face progressive Aβ-induced vasoconstriction in APOE ε3, while nNOS could represent the activation of NO-mediated plasticity strategies in the same group. Our results confirm previous findings that the APOE genotype is linked with different vascular responses to AD pathology.
    MeSH term(s) Humans ; Alzheimer Disease/genetics ; Apolipoprotein E3 ; Apolipoprotein E4/genetics ; Amyloidogenic Proteins ; Genotype ; Protein Isoforms
    Chemical Substances Apolipoprotein E3 ; Apolipoprotein E4 ; Amyloidogenic Proteins ; Protein Isoforms
    Language English
    Publishing date 2024-03-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25073725
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  4. Article ; Online: Correction to: Circulating calprotectin as a supporting inflammatory marker in discriminating SARS-CoV-2 infection: an observational study.

    Cherubini, Fabio / Cristiano, Antonio / Valentini, Alessandra / Bernardini, Sergio / Nuccetelli, Marzia

    Inflammation research : official journal of the European Histamine Research Society ... [et al.

    2021  Volume 71, Issue 1, Page(s) 1–8

    Language English
    Publishing date 2021-11-18
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 1221794-3
    ISSN 1420-908X ; 1023-3830
    ISSN (online) 1420-908X
    ISSN 1023-3830
    DOI 10.1007/s00011-021-01512-8
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  5. Article ; Online: Importance of nasal secretions in the evaluation of mucosal immunity elicited by mRNA BNT162b2 COVID-19 Vaccine.

    Francavilla, Beatrice / Nuccetelli, Marzia / Guerrieri, Mariapia / Fiorelli, Denise / Di Girolamo, Stefano

    EBioMedicine

    2022  Volume 79, Page(s) 104006

    MeSH term(s) Antibodies, Viral ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Immunity, Mucosal ; RNA, Messenger/genetics
    Chemical Substances Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; BNT162 Vaccine (N38TVC63NU)
    Language English
    Publishing date 2022-04-14
    Publishing country Netherlands
    Document type Letter ; Comment
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2022.104006
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  6. Article ; Online: Combined anti-SARS-CoV-2 IgA, IgG, and IgM Detection as a Better Strategy to Prevent Second Infection Spreading Waves.

    Nuccetelli, Marzia / Pieri, Massimo / Gisone, Francesca / Bernardini, Sergio

    Immunological investigations

    2020  Volume 51, Issue 2, Page(s) 233–245

    Abstract: Coronavirus disease (COVID-19) is challenging many health, economic, and social systems. RT-PCR assays are diagnosis gold standard; however, they can lead to false-negative results. Therefore, anti-SARS-CoV-2 IgG, IgM, and IgA investigation can play a ... ...

    Abstract Coronavirus disease (COVID-19) is challenging many health, economic, and social systems. RT-PCR assays are diagnosis gold standard; however, they can lead to false-negative results. Therefore, anti-SARS-CoV-2 IgG, IgM, and IgA investigation can play a complementary role in assessing the individuals immune status. Majority of serological tests focus on IgM and IgG although IgA are the main immunoglobulins involved in mucosal immunity. It has been reported that digestive symptoms may occur in the absence of any typical respiratory symptom. Thus, a complete screening, comprising IgA, IgM, and IgG detection could be more consistent and useful in patients with atypical symptoms or in paucisymptomatic cases. Current literature describes over 200 immunoassays available worldwide, pointing out a great results variability, depending on methodology or antigens' nature. In our study we evaluated anti-SARS-CoV-2 IgA, IgM, and IgG trend on a control group and on two COVID-19 patient groups (early and late infection time) with a lateral-flow combined immunoassay (LFIA) and an enzyme-linked immunosorbent assay (ELISA). Dissimilar antibodies time kinetics have been described in COVID-19 (decreasing IgM concentration with IgA/IgG persistence for a longer time; as well as persistent IgA, IgG, and IgM concentration); our results confirmed both of them depending on the methodology; therefore, it is difficult to compare different studies outcomes, suggesting the importance of a serological tests international standardization. Nevertheless, we propose a flowchart with combined anti-SARS-CoV-2 IgG/IgM/IgA detection as a screening on general population, where serological positivity should be considered as an "alert," to avoid and contain possible new outbreaks.
    MeSH term(s) Antibodies, Viral ; COVID-19 ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; SARS-CoV-2 ; Sensitivity and Specificity
    Chemical Substances Antibodies, Viral ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M
    Keywords covid19
    Language English
    Publishing date 2020-09-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 632565-8
    ISSN 1532-4311 ; 0882-0139
    ISSN (online) 1532-4311
    ISSN 0882-0139
    DOI 10.1080/08820139.2020.1823407
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    Zs.A 988: Show issues Location:
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  7. Article ; Online: Circulating calprotectin as a supporting inflammatory marker in discriminating SARS-CoV-2 infection: an observational study.

    Cherubini, Fabio / Cristiano, Antonio / Valentini, Alessandra / Bernardini, Sergio / Nuccetelli, Marzia

    Inflammation research : official journal of the European Histamine Research Society ... [et al.

    2021  Volume 70, Issue 6, Page(s) 687–694

    Abstract: Objective and design: Fecal calprotectin (CLP) is widely known for its detection in stools of patients with inflammatory bowel diseases (IBDs), to investigate the intestinal inflammatory status. Current research is promoting the circulating protein role ...

    Abstract Objective and design: Fecal calprotectin (CLP) is widely known for its detection in stools of patients with inflammatory bowel diseases (IBDs), to investigate the intestinal inflammatory status. Current research is promoting the circulating protein role as a systemic inflammatory marker. However, most studies report serum calprotectin analysis although plasma assay prevents its massive release by granulocytes. In this perspective, the ongoing SARS-CoV-2 pandemic deserves deployment of convenient and easy-to-dose markers that could reliably address the state of infection.
    Methods: We analyzed serum circulating calprotectin (cCLP) levels in hospitalized COVID-19 patients and plasma cCLP levels from patients with suspected SARS-CoV-2 infection, then assessed negative or positive on molecular tests.
    Results: Our results confirm a significant circulating calprotectin increase in infected subjects respect to controls, in serum and plasma. Moreover, plasma calprotectin has higher levels in suspected patients with positive SARS-CoV-2-RT-PCR, compared to suspected patients with negative SARS-CoV-2-RT-PCR. Furthermore, ROC curves results showed the circulating plasma calprotectin discriminatory ability to differentiate infected SARS-CoV-2 patients at a cutoff value greater than 131.3 ng/ml.
    Conclusions: Our data propose circulating calprotectin as a new, quantitative and predictive marker, which in addition to being an interesting generic inflammatory marker may provide important indications in SARS-CoV-2 infection.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; COVID-19/blood ; COVID-19/diagnosis ; COVID-19 Testing ; Female ; Humans ; Inflammation/blood ; Inflammation/diagnosis ; Leukocyte L1 Antigen Complex/blood ; Male ; Middle Aged ; Real-Time Polymerase Chain Reaction ; SARS-CoV-2
    Chemical Substances Biomarkers ; Leukocyte L1 Antigen Complex
    Language English
    Publishing date 2021-05-06
    Publishing country Switzerland
    Document type Journal Article ; Observational Study
    ZDB-ID 1221794-3
    ISSN 1420-908X ; 1023-3830
    ISSN (online) 1420-908X
    ISSN 1023-3830
    DOI 10.1007/s00011-021-01465-y
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  8. Article ; Online: Evaluation of the accuracy in the mucosal detection of anti-SARS-CoV-2 antibodies in nasal secretions and saliva.

    Fiorelli, Denise / Francavilla, Beatrice / Magrini, Andrea / Di Girolamo, Stefano / Bernardini, Sergio / Nuccetelli, Marzia

    International immunopharmacology

    2022  Volume 115, Page(s) 109615

    Abstract: COVID-19 vaccination with mRNA vaccines induces immune responses capable of neutralizing SARS-CoV-2. Commercially available serological anti-SARS-CoV-2 quantitative and neutralizing assays are essential for the determination of immune responses to ... ...

    Abstract COVID-19 vaccination with mRNA vaccines induces immune responses capable of neutralizing SARS-CoV-2. Commercially available serological anti-SARS-CoV-2 quantitative and neutralizing assays are essential for the determination of immune responses to vaccines. Nevertheless, at present there is a lack of validated tests to assess the mucosal response to COVID-19 vaccination and standardized analytic and pre-analytic methods have not yet been defined. The aim of our study was to evaluate the accuracy of two diagnostic immunoassays for COVID-19 (ELISA for IgA-S1 and chemiluminescent assay for IgG-RBD) on serum, saliva, and nasal secretions, by the enrollment of three study populations (healthy controls, vaccinated subjects, and subjects recovered from COVID-19 infection). In order to obtain an appropriate cut-off value for the biological matrices studied, ROC curve analyses were performed. Data demonstrate that the analytical and pre-analytical method we have developed can provide accurate and reliable results for the detection of anti-SARS-CoV-2 mucosal specific antibodies (IgA-S1 and IgG-RBD) on saliva and, as a novelty, on nasal secretions, either after COVID-19 infection or in vaccinated subjects.
    MeSH term(s) Humans ; Saliva ; COVID-19/diagnosis ; COVID-19 Vaccines ; SARS-CoV-2 ; Antibodies, Viral ; Immunoglobulin A ; Immunoglobulin G ; Antibodies, Neutralizing
    Chemical Substances COVID-19 Vaccines ; Antibodies, Viral ; Immunoglobulin A ; Immunoglobulin G ; Antibodies, Neutralizing
    Language English
    Publishing date 2022-12-20
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2043785-7
    ISSN 1878-1705 ; 1567-5769
    ISSN (online) 1878-1705
    ISSN 1567-5769
    DOI 10.1016/j.intimp.2022.109615
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  9. Article: The Antibodies' Response to SARS-CoV-2 Vaccination: 1-Year Follow Up.

    Nicolai, Eleonora / Tomassetti, Flaminia / Pelagalli, Martina / Sarubbi, Serena / Minieri, Marilena / Nisini, Alberto / Nuccetelli, Marzia / Ciotti, Marco / Pieri, Massimo / Bernardini, Sergio

    Biomedicines

    2023  Volume 11, Issue 10

    Abstract: The use of vaccines has allowed the containment of coronavirus disease 2019 (COVID-19) at a global level. The present work aims to add data on vaccination by evaluating the level of neutralizing antibodies in individuals who have received a three- ... ...

    Abstract The use of vaccines has allowed the containment of coronavirus disease 2019 (COVID-19) at a global level. The present work aims to add data on vaccination by evaluating the level of neutralizing antibodies in individuals who have received a three-vaccination series. For this purpose, we ran a surveillance program directed at measuring the level of IgG Abs against the Receptor Binding Domain (RBD) and surrogate virus neutralizing Ab (sVNT) anti-SARS-CoV-2 in the serum of individuals undergoing vaccination. This study was performed on employees from the University of Rome Tor Vergata and healthcare workers from the University Hospital who received the Vaxzevria vaccine (n = 56) and Comirnaty vaccine (n = 113), respectively. After the second dose, an increase in both RBD and sVNT Ab values was registered. In individuals who received the Comirnaty vaccine, the antibody titer was about one order of magnitude higher after 6 months from the first dose. All participants in this study received the Comirnaty vaccine as the third dose, which boosted the antibody response. Five months after the third dose, nearly one year from the first injection, the antibody level was >1000 BAU/mL (binding antibody units/mL). According to the values reported in the literature conferring protection against SARS-CoV-2 infection, our data indicate that individuals undergoing three vaccine doses present a low risk of infection.
    Language English
    Publishing date 2023-09-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11102661
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  10. Article ; Online: Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes.

    Cristiano, Antonio / Belardi, Riccardo / Hajrullaj, Hajro / Fabiani, Emiliano / Falconi, Giulia / Galossi, Elisa / Bernardini, Sergio / Voso, Maria Teresa / Nuccetelli, Marzia

    Inflammation research : official journal of the European Histamine Research Society ... [et al.

    2023  Volume 72, Issue 8, Page(s) 1695–1707

    Abstract: Objective and design: Systemic-Inflammatory-Autoimmune-Diseases (SIAD) is increasingly considered in Myelodysplastic-Syndromes (MDS). In this line, we evaluated the MDS auto-immunological profile, correlating it to the mutational landscape, trying to ... ...

    Abstract Objective and design: Systemic-Inflammatory-Autoimmune-Diseases (SIAD) is increasingly considered in Myelodysplastic-Syndromes (MDS). In this line, we evaluated the MDS auto-immunological profile, correlating it to the mutational landscape, trying to identify a molecular-genetic trigger agent related to SIAD.
    Methods and materials: Eighty-one MDS were enrolled and t-NGS was performed. Anti-Nuclear-Antibodies (ANA) were tested, and ANA-antigenic-specificity was characterized by ANA-profile, ENA-screen, anti-dsDNA. Non-Hematological-Patients (NHP) and Healthy-Donors (HD) were used as controls.
    Results: At clinically relevant cut-off (≥ 1:160), ANA was significantly more frequent in MDS, while ANA-antigenic-specificity showed a low association rate. ANA ≥ 1:160-positive MDS showed a mutational landscape similar to ANA-negative/ANA < 1:160 MDS. No significant correlations between mutational and immunological profiles were found and UBA1 mutations, related to VEXAS, were absent.
    Conclusions: Although ANA-positivity was found to be increased in MDS, the low ANA-antigenic-specificity suggests that autoantibodies didn't recognize autoimmune-pathognomonic antigens. The lack of relationship between genetic profile and ANA-positivity, suggests that MDS genetic variants may not be the direct cause of SIAD.
    MeSH term(s) Humans ; Autoantibodies ; Antibodies, Antinuclear ; Mutation ; Myelodysplastic Syndromes/genetics
    Chemical Substances Autoantibodies ; Antibodies, Antinuclear
    Language English
    Publishing date 2023-07-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1221794-3
    ISSN 1420-908X ; 1023-3830
    ISSN (online) 1420-908X
    ISSN 1023-3830
    DOI 10.1007/s00011-023-01773-5
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