المؤلفون: Gremese, Elisa, Alivernini, Stefano, Ferraccioli, Gianfranco

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2021 May . 118(20), 1-2.

الوصول الحر: https://www.jstor.org/stable/27040378Test

المؤلفون: Gremese, Elisa, Ferraccioli, Gianfranco

مصطلحات موضوعية: Correspondence

وصف الملف: text/html

العلاقة: http://ard.bmj.com/cgi/content/short/82/7/e157Test; http://dx.doi.org/10.1136/annrheumdis-2021-220932Test

الإتاحة: https://doi.org/10.1136/annrheumdis-2021-220932Test
http://ard.bmj.com/cgi/content/short/82/7/e157Test

المؤلفون: Gremese, Elisa, Tolusso, Barbara, Bruno, Dario, Paglionico, Anna Maria, Perniola, Simone, Ferraccioli, Gianfranco, Alivernini, Stefano

المصدر: European Journal of Clinical Investigation ; volume 53, issue 12 ; ISSN 0014-2972 1365-2362

الوصف: Background The SARS‐CoV‐2 pandemic has led to more than 6,870.000 deaths worldwide. Despite recent therapeutic advances, deaths in Intensive Care Units still range between 34 and 72%, comprising substantial unmet need as we move to an endemic phase. The general agreement is that in the first few days of infection, antiviral drugs and neutralizing monoclonal antibodies should be adopted. When the patient is hospitalized and develops severe pneumonia, progressing to a systemic disease, immune modifying therapy with corticosteroids is indicated. Such interventions, however, are less effective in the context of comorbidities (e.g., diabetes, hypertension, heart failure, atrial fibrillation, obesity and central nervous system‐CNS diseases) which are by themselves associated with poor outcomes. Such comorbidities comprise common and some distinct underlying inflammatory pathobiology regulated by differential cytokine taxonomy. Methods Searching in the PubMed database, literature pertaining to the biology underlying the different comorbidities, and the data from the studies related to various immunological treatments for the Covid‐19 disease were carefully analyzed. Results Several experimental and clinical data have demonstrated that hypertension and atrial fibrillation present an IL‐6 dependent signature, whereas diabetes, obesity, heart failure and CNS diseases may exhibit an IL‐1a/b predominant signature. Distinct selective cytokine targeting may offer advantage in treating severe COVID‐19 illness based on single or multiple associated comorbidities. When the patient does not immediately respond, a broader target range through JAKs pathway inhibitors may be indicated. Conclusions Herein, we discuss the biological background associated with distinct comorbidities which might impact the SARS‐CoV‐2 infection course and how these should to be addressed to improve the current therapeutic outcome.

الإتاحة: https://doi.org/10.1111/eci.14096Test

المؤلفون: Ferraccioli, Gianfranco, Zanardi, Romeo, Gremese, Elisa

المصدر: RMD Open ; volume 9, issue 2, page e003017 ; ISSN 2056-5933

مصطلحات موضوعية: Immunology, Immunology and Allergy, Rheumatology

الوصف: Chondrocalcinosis (CC) is the one of the most common crystal pyrophosphate disease associated arthritis in the elderly. It has been shown to coexist with seronegative and seropositive rheumatoid arthritis (RA), yet mostly with seronegative RA. Among the localisation of CC, the deposition in the ligaments surrounding the odontoid process may remain asymptomatic for years or may lead to and acute severe symptomatology, which may mimic several clinical illnesses among which meningitis (fever, severe pain, acute phase reactants). This is called the ‘crowned dens syndrome (CDS)’, which has been reported to represent an important percentage of acute neck pain needing hospital admission in neurosurgery units. In this case, the rapid demonstration of ‘crowned dens’ through CT scan may allow to avoid lumbar puncture and cerebrospinal fluid examination. The coexistence of RA and CDS is very rare, and rarely reported in the literature, yet it may represent a clinical challenge. We describe here one case that while on therapy with methotrexate (MTX) and naproxen (NPX) had an acute neck pain, and peripheral arthritis flare, that responded well to colchicine given along with MTX and NPX.

الإتاحة: https://doi.org/10.1136/rmdopen-2023-003017Test

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

المصدر: Frontiers in Medicine ; volume 10 ; ISSN 2296-858X

الوصف: 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 in vivo animal models and the effectiveness of biologic-Disease Modifying Anti-Rheumatic Drugs (b-DMARDs) in patients with RA. However, additional inflammatory soluble mediators such as IL-8 and IL-17 exert their pathogenetic actions promoting the detrimental activation of immune and stromal cells in RA synovial membrane, tendons, and extra-articular sites, as well as blood vessels and lungs, causing extra-articular complications, which might be excluded by the action of anti-TNFα and anti-IL6R targeted therapies. In this narrative review, we will discuss the role of IL-8 and IL-17 in promoting inflammation in multiple biological compartments (i.e., synovial membrane, blood vessels, and lung, respectively) in animal models of arthritis and patients with RA and how their selective targeting could improve the management of treatment resistance in patients.

الإتاحة: https://doi.org/10.3389/fmed.2023.956127Test

المؤلفون: Scagnellato, Laura, Collesei, Antonio, Doria, Andrea, Cozzi, Giacomo, Lorenzin, Mariagrazia, Atzeni, Fabiola, Bugatti, Serena, Caporali, Roberto, Cauli, Alberto, Conti, Fabrizio, Corrado, Addolorata, Carletto, Antonio, Chimenti, Maria Sole, Foti, Rosario, Frediani, Bruno, Gerli, Roberto, Gorla, Roberto, Govoni, Marcello, Gremese, Elisa, Guiducci, Serena, Iagnocco, Annamaria, Iannone, Florenzo, Parisi, Simone, Rossini, Maurizio, Salaffi, Fausto, Santo, Leonardo, Sarzi Puttini, Piercarlo, Sebastiani, Marco, Semerano, Angelo, Ferraccioli, Gianfranco, Lapadula, Giovanni, Ramonda, Roberta

المساهمون: Scagnellato, Laura, Collesei, Antonio, Doria, Andrea, Cozzi, Giacomo, Lorenzin, Mariagrazia, Atzeni, Fabiola, Bugatti, Serena, Caporali, Roberto, Cauli, Alberto, Conti, Fabrizio, Corrado, Addolorata, Carletto, Antonio, Chimenti, Maria Sole, Foti, Rosario, Frediani, Bruno, Gerli, Roberto, Gorla, Roberto, Govoni, Marcello, Gremese, Elisa, Guiducci, Serena, Iagnocco, Annamaria, Iannone, Florenzo, Parisi, Simone, Rossini, Maurizio, Salaffi, Fausto, Santo, Leonardo, Sarzi Puttini, Piercarlo, Sebastiani, Marco, Semerano, Angelo, Ferraccioli, Gianfranco, Lapadula, Giovanni, Ramonda, Roberta

مصطلحات موضوعية: comorbiditie, spondyloarthriti, tumour necrosis factor-α inhibitor, anti-interleukin, cardiovascular disease, haematological malignancy, solid cancer, gastrointestinal disorder, fibromyalgia

الوصف: Objectives: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. Methods: SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance. Results: The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities. Conclusions: Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37650298; volume:42; issue:1; firstpage:104; lastpage:114; numberofpages:11; journal:CLINICAL AND EXPERIMENTAL RHEUMATOLOGY; https://hdl.handle.net/11573/1706050Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85184279128

الإتاحة: https://doi.org/10.55563/clinexprheumatol/q38lu0Test
https://hdl.handle.net/11573/1706050Test

المؤلفون: Gremese, Elisa, Tolusso, Barbara, Petricca, Luca, Di Mario, Clara, Ferraccioli, Gianfranco, Alivernini, Stefano

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

مصطلحات موضوعية: Biomarkers, CTLA4-Ig, Rheumatoid arthritis, Abatacept, CTLA-4 Antigen, Cytokines, Forkhead Transcription Factors, Humans, Interleukin-6, STAT5 Transcription Factor, T-Lymphocytes, Regulatory, Antirheumatic Agents, Arthritis, Rheumatoid, Settore MED/16 - REUMATOLOGIA

الوصف: Background Prognostic biomarkers of treatment response to distinct biologic disease-modifying anti-rheumatic drugs (b-DMARDs) are still lacking within the management of rheumatoid arthritis (RA). Methods Thirty-four b-DMARDs naive RA patients, divided by disease duration into early (cohort 1) and long standing (cohort 2), received CTLA4-Ig. At study entry, and every 3 months for 1 year, each patient underwent peripheral blood (PB)-derived CD4(pos) cell subpopulation assessment by flow cytometry, STAT3 and STAT5 expression by RT-PCR and IL-6, IL-12p70, TGF beta, and IL-10 serum levels by ELISA. The DAS and CDAI remission was assessed at 6 and 12 months. Results DAS- and CDAI-defined remission within 12 months was achieved by 16 (47.1%) and 8 (23.5%) RA patients, respectively. Considering the whole RA cohort, CTLA4-Ig induced a significant decrease of IL-6 serum levels from baseline to 6 and 12 months, as well as of PB CD4(pos)CD25(pos)FoxP3(pos) cells at 6 and 12 months, and of CD4(pos)IL17(pos) cells after 12 months. PB CD4(pos) cells of RA patients showed higher STAT3 and STAT5 expression than healthy controls, which remained unchanged within 12 months of treatment. At study entry, RA patients achieving DAS remission had significantly lower IL-6 serum levels than RA patients not achieving this outcome. In particular, having baseline IL-6 serum levels <= 8.4 pg/ml, significantly identified naive to b-DMARDs RA patients more likely to achieve DAS-remission under CTLA4-Ig at 6 months (66.7%) compared to RA patients with baseline IL-6 serum levels > 8.4 pg/ml [15.4%, OR (95%Cis) 11.00 (1.75-55.82)]. Moreover, having CD4(pos)CD25(pos)FoxP3(pos) cells rate >= 6.0% significantly identifies naive to b-DMARDs early RA patients more likely to achieve DAS remission at 6 months (83.3%) compared to RA patients with baseline CD4(pos)CD25(pos)FoxP3(pos) cells < 6.0% [16.7%, OR (95% Cis) 25.00 (1.00-336.81)]. Conclusions Baseline IL-6 serum levels and peripheral blood-derived CD4(pos) subpopulations are putative ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35706043; info:eu-repo/semantics/altIdentifier/wos/WOS:000812789700001; volume:24; issue:1; firstpage:143; lastpage:N/A; issueyear:N/A; journal:ARTHRITIS RESEARCH & THERAPY; https://hdl.handle.net/10807/220068Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85131940729

الإتاحة: https://doi.org/10.1186/s13075-022-02827-5Test
https://hdl.handle.net/10807/220068Test

المؤلفون: Gremese, Elisa, Bruno, Dario, Nagy, György, Ferraccioli, Gianfranco

المصدر: European Journal of Internal Medicine ; ISSN 0953-6205

مصطلحات موضوعية: Internal Medicine

الإتاحة: https://doi.org/10.1016/j.ejim.2024.01.019Test
https://api.elsevier.com/content/article/PII:S0953620524000281?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0953620524000281?httpAccept=text/plainTest

المؤلفون: Gremese, Elisa, Bruno, Dario, Ferraccioli, Gianfranco

المصدر: European Journal of Internal Medicine ; volume 119, page 125-126 ; ISSN 0953-6205

مصطلحات موضوعية: Internal Medicine

الإتاحة: https://doi.org/10.1016/j.ejim.2023.09.019Test
https://api.elsevier.com/content/article/PII:S0953620523003394?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0953620523003394?httpAccept=text/plainTest

المؤلفون: Bruno, Dario, Tolusso, Barbara, Lugli, Gianmarco, Di Mario, Clara, Petricca, Luca, Perniola, Simone, Bui, Laura, Benvenuto, Roberta, Ferraccioli, Gianfranco, Alivernini, Stefano, Gremese, Elisa

المصدر: International Journal of Molecular Sciences; Mar2024, Vol. 25 Issue 6, p3259, 15p

مصطلحات موضوعية: TALL-1 (Protein), SALIVARY glands, INTERLEUKIN receptors, NON-Hodgkin's lymphoma, BIOMARKERS, HOCKEY

مستخلص: Primary Sjögren's disease is primarily driven by B-cell activation and is associated with a high risk of developing non-Hodgkin's lymphoma (NHL). Over the last few decades, microRNA-155 (miR-155) has arisen as a key regulator of B-cells. Nevertheless, its role in primary Sjögren's disease remains elusive. Thus, the purpose of this study was (i) to explore miR-155, B-cell activating factor (BAFF)-receptor (BAFF-R), and Interleukin 6 receptor (IL-6R) expression in the labial salivary glands (LSG) of patients with primary Sjögren's disease, aiming to identify potential B-cell activation biomarkers related to NHL development. Twenty-four patients with primary Sjögren's disease, and with available tissue blocks from a LSG biopsy performed at diagnosis, were enrolled. Among them, five patients developed B-cell NHL during follow-up (7.3 ± 3.1 years). A comparison group of 20 individuals with sicca disease was included. Clinical and laboratory parameters were recorded and the LSG biopsies were evaluated to assess local inflammation in terms of miR-155/BAFF-R and IL-6R expression. Stratifying the primary Sjögren's disease cohort according to lymphomagenesis, miR-155 was upregulated in primary Sjögren's disease patients who experienced NHL, more so than those who did not experience NHL. Moreover, miR-155 expression correlated with the focus score (FS), as well as BAFF-R and IL-6R expression, which were increased in primary Sjögren's disease patients and in turn related to neoplastic evolution. In conclusion, epigenetic modulation may play a crucial role in the aberrant activation of B-cells in primary Sjögren's disease, profoundly impacting the risk of NHL development. [ABSTRACT FROM AUTHOR]

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