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  1. Article ; Online: Using explainable artificial intelligence to predict and forestall flare in rheumatoid arthritis.

    Alivernini, Stefano / Cañete, Juan D / Bacardit, Jaume / Kurowska-Stolarska, Mariola

    Nature medicine

    2024  Volume 30, Issue 4, Page(s) 925–926

    MeSH term(s) Humans ; Artificial Intelligence ; Arthritis, Rheumatoid/drug therapy ; Antirheumatic Agents/therapeutic use
    Chemical Substances Antirheumatic Agents
    Language English
    Publishing date 2024-02-15
    Publishing country United States
    Document type Letter
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-024-02818-w
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  2. Article ; Online: Synovial tissue macrophages in joint homeostasis, rheumatoid arthritis and disease remission.

    Kurowska-Stolarska, Mariola / Alivernini, Stefano

    Nature reviews. Rheumatology

    2022  Volume 18, Issue 7, Page(s) 384–397

    Abstract: Synovial tissue macrophages (STMs) were principally recognized as having a pro-inflammatory role in rheumatoid arthritis (RA), serving as the main producers of pathogenic tumour necrosis factor (TNF). Recent advances in single-cell omics have facilitated ...

    Abstract Synovial tissue macrophages (STMs) were principally recognized as having a pro-inflammatory role in rheumatoid arthritis (RA), serving as the main producers of pathogenic tumour necrosis factor (TNF). Recent advances in single-cell omics have facilitated the discovery of distinct STM populations, providing an atlas of discrete phenotypic clusters in the context of healthy and inflamed joints. Interrogation of the functions of distinct STM populations, via ex vivo and experimental mouse models, has re-defined our understanding of STM biology, opening up new opportunities to better understand the pathology of the arthritic joint. These works have identified STM subpopulations that form a protective lining barrier within the synovial membrane and actively participate in the remission of RA. We discuss how distinct functions of STM clusters shape the synovial tissue environment in health, during inflammation and in disease remission, as well as how an increased understanding of STM heterogeneity might aid the prediction of clinical outcomes and inform novel treatments for RA.
    MeSH term(s) Animals ; Arthritis, Rheumatoid/pathology ; Homeostasis ; Humans ; Inflammation/pathology ; Macrophages/pathology ; Mice ; Synovial Membrane/pathology
    Language English
    Publishing date 2022-06-07
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2491532-4
    ISSN 1759-4804 ; 1759-4790
    ISSN (online) 1759-4804
    ISSN 1759-4790
    DOI 10.1038/s41584-022-00790-8
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  3. Article: Editorial: Advance in B-cell therapies for the treatment of rheumatic and musculoskeletal diseases.

    Md Yusof, Md Yuzaiful / Alivernini, Stefano / Chatzidionysiou, Katerina

    Frontiers in medicine

    2022  Volume 9, Page(s) 1020859

    Language English
    Publishing date 2022-09-21
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2022.1020859
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  4. Article ; Online: The pathogenesis of rheumatoid arthritis.

    Alivernini, Stefano / Firestein, Gary S / McInnes, Iain B

    Immunity

    2022  Volume 55, Issue 12, Page(s) 2255–2270

    Abstract: Significant recent progress in understanding rheumatoid arthritis (RA) pathogenesis has led to improved treatment and quality of life. The introduction of targeted-biologic and -synthetic disease modifying anti-rheumatic drugs (DMARDs) has also ... ...

    Abstract Significant recent progress in understanding rheumatoid arthritis (RA) pathogenesis has led to improved treatment and quality of life. The introduction of targeted-biologic and -synthetic disease modifying anti-rheumatic drugs (DMARDs) has also transformed clinical outcomes. Despite this, RA remains a life-long disease without a cure. Unmet needs include partial response and non-response to treatment in many patients, failure to achieve immune homeostasis or drug free remission, and inability to repair damaged tissues. RA is now recognized as the end of a multi-year prodromal phase in which systemic immune dysregulation, likely beginning in mucosal surfaces, is followed by a symptomatic clinical phase. Inflammation and immune reactivity are primarily localized to the synovium leading to pain and articular damage, but is also associated with a broader series of comorbidities. Here, we review recently described immunologic mechanisms that drive breach of tolerance, chronic synovitis, and remission.
    MeSH term(s) Humans ; Quality of Life ; Arthritis, Rheumatoid/drug therapy ; Antirheumatic Agents/therapeutic use ; Synovitis ; Synovial Membrane
    Chemical Substances Antirheumatic Agents
    Language English
    Publishing date 2022-12-12
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2022.11.009
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  5. Article: The forgotten key players in rheumatoid arthritis: IL-8 and IL-17 - Unmet needs and therapeutic perspectives.

    Gremese, Elisa / Tolusso, Barbara / Bruno, Dario / Perniola, Simone / Ferraccioli, Gianfranco / Alivernini, Stefano

    Frontiers in medicine

    2023  Volume 10, Page(s) 956127

    Abstract: Despite the relevant advances in our understanding of the pathogenetic mechanisms regulating inflammation in rheumatoid arthritis (RA) and the development of effective therapeutics, to date, there is still a proportion of patients with RA who do not ... ...

    Abstract Despite the relevant advances in our understanding of the pathogenetic mechanisms regulating inflammation in rheumatoid arthritis (RA) and the development of effective therapeutics, to date, there is still a proportion of patients with RA who do not respond to treatment and end up progressing toward the development of joint damage, extra-articular complications, and disability. This is mainly due to the inter-individual heterogeneity of the molecular and cellular taxonomy of the synovial membrane, which represents the target tissue of RA inflammation. Tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) are crucial key players in RA pathogenesis fueling the inflammatory cascade, as supported by experimental evidence derived from
    Language English
    Publishing date 2023-03-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.956127
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  6. Article ; Online: RAASI, NSAIDs, antidiabetics, and anticoagulants: More data needed to be labeled as harmful or neutral in SARS-CoV-2 infection.

    Gremese, Elisa / Alivernini, Stefano / Ferraccioli, Gianfranco

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 20

    MeSH term(s) Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Anticoagulants/therapeutic use ; COVID-19/drug therapy ; COVID-19/epidemiology ; COVID-19/pathology ; Humans ; Hypoglycemic Agents/therapeutic use ; Renin-Angiotensin System/drug effects ; SARS-CoV-2
    Chemical Substances Angiotensin-Converting Enzyme Inhibitors ; Anti-Inflammatory Agents, Non-Steroidal ; Anticoagulants ; Hypoglycemic Agents
    Language English
    Publishing date 2021-05-08
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2025609118
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  7. Article ; Online: The Role of Neutrophils in Spondyloarthritis: A Journey across the Spectrum of Disease Manifestations.

    Coletto, Lavinia Agra / Rizzo, Chiara / Guggino, Giuliana / Caporali, Roberto / Alivernini, Stefano / D'Agostino, Maria Antonietta

    International journal of molecular sciences

    2023  Volume 24, Issue 4

    Abstract: Spondyloarthritis (SpA) contemplates the inflammatory involvement of the musculoskeletal system, gut, skin, and eyes, delineating heterogeneous diseases with a common pathogenetic background. In the framework of innate and adaptive immune disruption in ... ...

    Abstract Spondyloarthritis (SpA) contemplates the inflammatory involvement of the musculoskeletal system, gut, skin, and eyes, delineating heterogeneous diseases with a common pathogenetic background. In the framework of innate and adaptive immune disruption in SpA, neutrophils are arising, across different clinical domains, as pivotal cells crucial in orchestrating the pro-inflammatory response, both at systemic and tissue levels. It has been suggested they act as key players along multiple stages of disease trajectory fueling type 3 immunity, with a significant impact in the initiation and amplification of inflammation as well as in structural damage occurrence, typical of long-standing disease. The aim of our review is to focus on neutrophils' role within the spectrum of SpA, dissecting their functions and abnormalities in each of the relevant disease domains to understand their rising appeal as potential biomarkers and therapeutic targets.
    MeSH term(s) Humans ; Neutrophils/pathology ; Spondylarthritis/pathology ; Inflammation ; Skin/pathology ; Eye/pathology
    Language English
    Publishing date 2023-02-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24044108
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  8. Article ; Online: A multiparametric risk table for loss of clinical remission status in patients with rheumatoid arthritis: A starter study post-hoc analysis.

    Perniola, Simone / Alivernini, Stefano / Gremese, Elisa / Landolfi, Gianpiero / Carrara, Greta / Iagnocco, Annamaria / Scirè, Carlo Alberto

    Rheumatology (Oxford, England)

    2024  

    Abstract: Objective: This post-hoc analysis was carried out on data acquired in the longitudinal Sonographic Tenosynovitis/arthritis Assessment in Rheumatoid Arthritis Patients in Remission (STARTER) study. Its primary aim was to determine the predictive clinical ...

    Abstract Objective: This post-hoc analysis was carried out on data acquired in the longitudinal Sonographic Tenosynovitis/arthritis Assessment in Rheumatoid Arthritis Patients in Remission (STARTER) study. Its primary aim was to determine the predictive clinical and MSUS features factors for disease flare in RA patients in clinical remission, whilst its secondary aim was to evaluate the probability of disease flare based on clinical and MSUS features.
    Methods: The analysis included a total of 389 RA patients in DAS28-defined remission. All patients underwent a MSUS examination according to OMERACT guidelines. Logistic regression and results presented as OR and 95%CI were used for the evaluation of the association between selected variables and disease flare. Significant clinical and MSUS features were incorporated into a risk table to predict disease flare within 12 months in RA remission patients.
    Results: Within 12 months, 137(35%) RA patients experienced a disease flare. RA patients who experienced a flare disease differed from persistent remission for ACPA positivity (75.9%vs62.3%; p= 0.007), percentage of sustained clinical remission at baseline (44.1%vs68.5%; p= 0.001) and synovium PD signal presence (58.4%vs33.3%; p< 0.001). Based on these results, the three features were considered in a predictive model of disease flare with adjOR 3.064(95%CI 1.728-5.432). Finally, a risk table was constructed including the three significant predictive factors of disease flare within 12 months from the enrolment.
    Conclusion: An adaptive flare prediction model tool, based on data available in outpatient setting, were developed as a multiparametric risk table. If confirmed by the external validation, this tool might support the definition of therapeutic strategies in RA patients in DAS28-defined remission status.
    Language English
    Publishing date 2024-02-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keae094
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  9. Article ; Online: Infectious agents breaking the immunological tolerance: The holy grail in rheumatoid arthritis reconsidered.

    Gremese, Elisa / Tolusso, Barbara / Bruno, Dario / Alivernini, Stefano / Ferraccioli, Gianfranco

    Autoimmunity reviews

    2022  Volume 21, Issue 6, Page(s) 103102

    Abstract: Multiple Sclerosis (MS) has been shown to be linked to Epstein Barr Virus (EBV) infection, a virus that infects B cells inside the CNS. The seminal study raises a key interest into the infectious origin of several other autoimmune inflammatory diseases ... ...

    Abstract Multiple Sclerosis (MS) has been shown to be linked to Epstein Barr Virus (EBV) infection, a virus that infects B cells inside the CNS. The seminal study raises a key interest into the infectious origin of several other autoimmune inflammatory diseases.We will discuss here the infectious agents that have been studied over the years in Rheumatoid Arthritis (RA), a crippling arthritis that was treated a century ago with gold salts (anti mycobacterial agent), chloroquine (anti malarial agent), or sulphasalazine (an antibacterial-antiinflammatory agent). Several infectious agents have been taken into consideration, i.e. Streptococcus group A, Proteus, Mycobacterium tuberculosis-MTB, Parvovirus B19, Epstein Barr virus, Porphyromonas gingivalis-Pg, Aggregatibacter actinomycetescomitans, and finally Haemophilus-Glaesserella parasuis-Hps. Of these agents only three satisfy the Witebski's criteria as possible pathogenetic causes of an autoimmune disease, i.e. MTB, Pg, Hps. We will discuss here how the immune tolerance might be broken, which could be the neoantigen or autoantigen involved, how the infectious agent was studied as a trigger capable of inducing arthritis in animal models. The preventive measures that should be adopted to lessen the impact of the infections, to prevent the burden and the severity of the illness are described.
    MeSH term(s) Animals ; Arthritis, Rheumatoid ; Autoimmune Diseases ; B-Lymphocytes ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Immune Tolerance
    Language English
    Publishing date 2022-04-19
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2144145-5
    ISSN 1873-0183 ; 1568-9972
    ISSN (online) 1873-0183
    ISSN 1568-9972
    DOI 10.1016/j.autrev.2022.103102
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  10. Article ; Online: Correction: Peripheral blood CD4

    Gremese, Elisa / Tolusso, Barbara / Petricca, Luca / Di Mario, Clara / Gigante, Maria Rita / Ferraccioli, Gianfranco / Alivernini, Stefano

    Arthritis research & therapy

    2022  Volume 24, Issue 1, Page(s) 177

    Language English
    Publishing date 2022-07-25
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2107602-9
    ISSN 1478-6362 ; 1478-6354
    ISSN (online) 1478-6362
    ISSN 1478-6354
    DOI 10.1186/s13075-022-02866-y
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