Publications by authors named "Francesca W Rossi"

11 Publications

  • Page 1 of 1

THE ROLE OF CHEST CT IN DECIPHERING INTERSTITIAL LUNG INVOLVEMENT: SYSTEMIC SCLEROSIS VERSUS COVID-19.

Rheumatology (Oxford) 2021 Jul 28. Epub 2021 Jul 28.

Department of Experimental and Clinical Medicine, University of Florence, and Infectious and TropicalDiseases Unit, AOUC, Florence, Italy.

Objective: To identify the main computed tomography (CT) features that may help distinguishing a progression of interstitial lung disease (ILD) secondary to Systemic sclerosis (SSc) from COVID-19 pneumonia.

Methods: This multicentric study included 22 international readers divided in the radiologist group (RAD) and non-radiologist group (nRAD). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study.

Results: Fibrosis inside focal ground glass opacities (GGO) in the upper lobes; fibrosis in the lower lobe GGO; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONS in the lower lobes (p < 0.0001) and signs of fibrosis in GGO in the lower lobes (p < 0.0001) remained independently associated with COVID-19 pneumonia or SSc-ILD, respectively. A predictive score was created which resulted positively associated with the COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity).

Conclusion: The CT differential diagnosis between COVID-19 pneumonia and SSc-ILD is possible through the combination the proposed score and the radiologic expertise. The presence of consolidation in the lower lobes may suggest a COVID-19 pneumonia while the presence of fibrosis inside GGO may indicate a SSc-ILD.
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http://dx.doi.org/10.1093/rheumatology/keab615DOI Listing
July 2021

Persistence of Mast Cell-Positive Synovitis in Early Rheumatoid Arthritis Following Treatment With Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs.

Front Pharmacol 2020 14;11:1051. Epub 2020 Jul 14.

Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

Mast cells (MCs) are immune cells infiltrating the synovial membrane and implicated in the pathogenesis of Rheumatoid Arthritis (RA). Their infiltration in the synovia of early RA patients has been shown to be associated with systemic inflammation, disease activity and autoantibody positivity. Here, we analyzed their presence in matched synovial samples obtained by ultrasound-guided synovial biopsies pre- and post-treatment with conventional synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs) (n=20). Upon IHC staining, patients were classified as MC based on the presence/absence of CD117+ synovial MCs. At baseline, MC patients had significantly higher synovial inflammation, inflammatory markers, disease activity and a higher prevalence of lympho-myeloid aggregates. Synovial biopsies after 6 months of treatment with csDMARDs showed a significant reduction of synovitis scores, but only a partial reduction of MC numbers. Accordingly, 45% of patients (9/20) were MC after treatment, in association with significantly higher degree of synovitis and higher proportion lympho-myeloid aggregates. Finally, significantly lower patients with MC synovitis at 6 months reached Low Disease Activity (LDA), while the association of MCs with disease activity was independent from lymphoid aggregates, after adjustment for BMI and age. Overall, this study confirms the relevance of MCs as part of the inflammatory infiltrate in the synovia of RA patients, warranting further investigations in larger cohorts to clarify their role in disease progression and response to treatment and their relevance as prognostic markers and potential therapeutic targets.
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http://dx.doi.org/10.3389/fphar.2020.01051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371927PMC
July 2020

Early Disease and Low Baseline Damage as Predictors of Response to Belimumab in Patients With Systemic Lupus Erythematosus in a Real-Life Setting.

Arthritis Rheumatol 2020 08 12;72(8):1314-1324. Epub 2020 Jun 12.

Università degli Studi di Genova, Genoa, Italy.

Objective: To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab.

Methods: In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results: The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years (OR 1.94 [95% CI 1.078-3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K (OR 14.59 [95% CI 3.54-59.79) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009).

Conclusion: In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.
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http://dx.doi.org/10.1002/art.41253DOI Listing
August 2020

Inflammatory, Serological and Vascular Determinants of Cardiovascular Disease in Systemic Lupus Erythematosus Patients.

Int J Mol Sci 2019 Apr 30;20(9). Epub 2019 Apr 30.

Department of Translational Medical Sciences, Federico II University, 80131 Naples, Italy.

Background And Aim: Systemic lupus erythematosus (SLE) is associated with increased risk of cardiovascular disease (CVD). Among many mechanisms, accelerated atherosclerosis, endothelial dysfunction, and hypercoagulability play a main role. Here, we investigate whether inflammatory, serological and clinical markers of SLE determine and correlate with arterial stiffness in SLE patients.

Materials And Methods: Routine blood samples, inflammatory mediators, specific antibodies, and 24 h proteinuria were measured in 43 SLE patients and 43 age and sex-matched controls using routine laboratory assays. We also assessed arterial stiffness by measuring radial artery applanation tonometry-derived augmentation index (AI), normalized AI ([email protected]), aortic pulse pressure, central systolic, diastolic and peripheral blood pressure.

Results: SLE patients showed a significantly greater arterial stiffness vs. controls, as demonstrated by the significantly higher [email protected] and aortic pulse pressure. Interestingly, regression analysis showed that age, systolic pulse pressure, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), daily dose of glucocorticoids, and cumulative organ damage positively correlated with arterial stiffness.

Conclusions: SLE patients show increased arterial stiffness which correlates with markers of inflammation, that is involved in early alterations in arterial walls. Applanation tonometry can be used to screen SLE patients for subclinical vascular damage to implement prevention strategies for CVD.
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http://dx.doi.org/10.3390/ijms20092154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540240PMC
April 2019

Urokinase type plasminogen activator receptor (uPAR) as a new therapeutic target in cancer.

Transl Med UniSa 2016 Nov 1;15:15-21. Epub 2016 Nov 1.

Department of Chemistry and Biology, University of Salerno, Salerno, Italy.

The urokinase (uPA)-type plasminogen activator receptor (uPAR) is a GPI-anchored receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. uPAR also regulates cell adhesion, migration and proliferation, protects from apoptosis and contributes to epithelial mesenchymal transition (EMT), independently of uPA enzymatic activity. Indeed, uPAR interacts with beta1, beta2 and beta3 integrins, thus regulating their activities. uPAR cross-talks with receptor tyrosine kinases through integrins and regulates cancer cell dormancy, proliferation and angiogenesis. Moreover, uPAR mediates uPA-dependent cell migration and chemotaxis induced by fMet-Leu-Phe (fMLF), through its association with fMLF-receptors (fMLF-Rs). Further, uPAR is an adhesion receptor because it binds vitronectin (VN), a component of provisional extracellular matrix. High uPAR expression predicts for more aggressive disease in several cancer types for its ability to increase invasion and metastasis. In fact, uPAR has been hypothesized to be the link between tumor cell dormancy and proliferation that usually precedes the onset of metastasis. Thus, inhibiting uPAR could be a feasible approach to affect tumor growth and metastasis. Here, we review the more recent advances in the development of uPAR-targeted anti-cancer therapeutic agents suitable for further optimization or ready for the evaluation in early clinical trials.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120746PMC
November 2016

67 kDa laminin receptor (67LR) in normal and neoplastic hematopoietic cells: is its targeting a feasible approach?

Transl Med UniSa 2016 Nov 1;15:8-14. Epub 2016 Nov 1.

Department of Medicine and Surgery, University of Salerno, Salerno, Italy.

The 67 kDa laminin receptor (67LR) is a non-integrin cell surface receptor for laminin (LM) that derives from a 37 kDa precursor (37LRP). 67LR expression is increased in neoplastic cells and correlates with an enhanced invasive and metastatic potentialin many human solid tumors, recommending this receptor as a new promising target for cancer therapy. This is supported by in vivo studies showing that 67LR downregulation reduces tumour cell proliferation and tumour formation by inducing apoptosis. 67LR association with the anti-apoptotic protein PED/PEA-15 activates a signal transduction pathway, leading to cell proliferation and resistance to apoptosis. However, the main function of 67LR is to enhance tumor cell adhesion to the LM of basement membranes and cell migration, two crucial events in the metastasis cascade. Thus, inhibition of 67LR binding to LM has been proved to be a feasible approach to block metastatic cancer cell spread. Despite accumulating evidences on 67LR overexpression in hematologic malignancies, 67LR role in these diseases has not been clearly defined. Here, we review 67LR expression and function in normal and malignant hematopoietic cells, 67LR role and prognostic impact in hematological malignancies and first attempts in targeting its activity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120745PMC
November 2016

PED/PEA-15 interacts with the 67 kD laminin receptor and regulates cell adhesion, migration, proliferation and apoptosis.

J Cell Mol Med 2012 Jul;16(7):1435-46

Department of Cellular and Molecular Biology and Pathology, Federico II University, Naples, taly.

Phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 kD (PED/PEA-15) is an anti-apoptotic protein whose expression is increased in several human cancers. In addition to apoptosis, PED/PEA-15 is involved in the regulation of other major cellular functions, including cell adhesion, migration, proliferation and glucose metabolism. To further understand the functions of this protein, we performed a yeast two-hybrid screening using PED/PEA-15 as a bait and identified the 67 kD high-affinity laminin receptor (67LR) as an interacting partner. 67 kD laminin receptor is a non-integrin cell-surface receptor for the extracellular matrix (ECM), derived from the dimerization of a 37 kD cytosolic precursor (37LRP). The 67LR is highly expressed in human cancers and widely recognized as a molecular marker of metastatic aggressiveness. The molecular interaction of PED/PEA-15 with 67LR was confirmed by pull-down experiments with recombinant His-tagged 37LRP on lysates of PED/PEA-15 transfected HEK-293 cells. Further, overexpressed or endogenous PED/PEA-15 was co-immunoprecipitated with 67LR in PED/PEA-15-transfected HEK-293 cells and in U-373 glioblastoma cells, respectively. PED/PEA-15 overexpression significantly increased 67LR-mediated HEK-293 cell adhesion and migration to laminin that, in turn, determined PED/PEA-15 phosphorylation both in Ser-104 and Ser-116, thus enabling cell proliferation and resistance to apoptosis. PED/PEA-15 ability to induce cell responses to ECM-derived signals through interaction with 67LR may be of crucial importance for tumour cell survival in a poor microenvironment, thus favouring the metastatic spread and colonization.
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http://dx.doi.org/10.1111/j.1582-4934.2011.01411.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823213PMC
July 2012

Human cardiac mast cells in anaphylaxis.

Chem Immunol Allergy 2010 1;95:98-109. Epub 2010 Jun 1.

Human heart mast cells (HHMC), by elaborating vasoactive mediators, cytokines and chemokines, are the main primary effector cells of anaphylaxis. Mast cells have been identified perivascularly, close to myocytes and in the arterial intima in human heart tissue. Mast cells isolated from human heart tissue (HHMC) of patients undergoing cardiac transplantation express high-affinity receptors for IgE (FcepsilonRI) and C5a receptors. Activation of HHMC in vitro with anti-IgE or anti-FcepsilonRI induced the release of preformed mediators (histamine, tryptase, chymase, and renin) and the de novo synthesis of LTC(4) (approximately =18 ng/l0(6) cells) and PGD(2) (approximately =18 ng/l0(6) cells). Complement is activated and anaphylatoxin forms during anaphylaxis. C5a causes rapid release of histamine and tryptase from HHMC. These cells are activated in vitro by therapeutic (general anesthetics, protamine, etc.) and diagnostic agents (radiocontrast media, etc.) which can cause anaphylactoid reactions. Low concentrations of histamine and cysteinyl leukotrienes given to subjects undergoing diagnostic catheterization caused significant systemic and coronary hemodynamic effects. These results indicate that HHMC probably have a role in anaphylactic reactions.
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http://dx.doi.org/10.1159/000315945DOI Listing
November 2010

Helicobacter pylori Hp(2-20) promotes migration and proliferation of gastric epithelial cells by interacting with formyl peptide receptors in vitro and accelerates gastric mucosal healing in vivo.

J Immunol 2009 Sep 19;183(6):3761-9. Epub 2009 Aug 19.

Divisione di Immunologia Clinica ed Allergologia e Centro Interdipartimentale di Ricerca di Scienze Immunologiche di Base e Cliniche, Università di Napoli Federico II, Naples, Italy.

Helicobacter pylori-derived peptide RpL1 aa 2-20 (Hp(2-20)) in addition to its antimicrobial action exerts several immunomodulatory effects in eukaryotic cells by interacting with formyl peptide receptors (FPRs). It has recently been shown that activation of FPRs facilitates intestinal epithelial cell restitution. We investigated whether Hp(2-20) induces healing of injured gastric mucosa and assessed the mechanisms underlying any such effect. We investigated the expression of FPRs in two gastric epithelial cell lines (MKN-28 and AGS) at mRNA and protein level. To determine whether FPRs were functional we performed chemotaxis experiments and proliferation assays and studied the Hp(2-20)-activated downstream signaling pathway. The effect of Hp(2-20) on mucosal healing was evaluated in rats after indomethacin-induced injury. Here we show that: (1) FPRs were expressed in both cell lines; (2) Hp(2-20) stimulated migration and proliferation of gastric epithelial cells; (3) this effect was specifically mediated by formyl peptide receptor-like 1 (FPRL1) and FPRL2 and was associated with activation of FPR-related downstream signaling pathways; (4) Hp(2-20) up-regulated the expression and secretion of vascular endothelial growth factor; and (5) Hp(2-20) accelerated healing of rat gastric mucosa after injury brought about by indomethacin at both the macroscopic and microscopic levels. In conclusion, by interacting with FRPL1 and FPRL2, H. pylori-derived Hp(2-20) induces cell migration and proliferation, as well as the expression of vascular endothelial growth factor, thereby promoting gastric mucosal healing. This study provides further evidence of the complexity of the relationship between H. pylori and human gastric mucosa, and it suggests that a bacterial product may be used to heal gastric mucosal injury.
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http://dx.doi.org/10.4049/jimmunol.0900863DOI Listing
September 2009

Role of superallergens in allergic disorders.

Chem Immunol Allergy 2007 ;93:195-213

Department of Clinical Immunology and Allergy, Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, School of Medicine, Naples, Italy.

A significant percentage of allergic diseases (e.g. certain cases of intrinsic asthma, chronic idiopathic urticaria, and atopic dermatitis) cannot be explained by the classical mechanisms of IgE/allergen-mediated activation of basophils and mast cells. We found that protein Fv, an endogenous protein synthesized in the human liver and increased during viral hepatitis, act as a superallergen by binding to IgE of the VH3 family and activating human basophils and mast cells. Similarly, envelope gp120 of HIV-1 and protein A of Staphylococcus aureus are viral and bacterial superallergens, respectively, because they interact with IgE VH3+. Protein L binds to the V domain of he kappa light chains of IgE. Our results demonstrate that endogenous, viral and bacterial products activate primary effector cells of allergic disorders to release proinflammatory mediators and cytokines thereby acting as immunoglobulin superantigens (superallergens).
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http://dx.doi.org/10.1159/000100896DOI Listing
May 2007

The human heart as a shock organ in anaphylaxis.

Novartis Found Symp 2004 ;257:133-49; discussion 149-60, 276-85

Department of Clinical Immunology and Allergy, University of Naples Federico II, School of Medicine, Via S. Pansini 5, 80131 Naples, Italy.

Human mast cells, by elaborating vasoactive mediators and cytokines, are the primary effector cells of anaphylaxis. A body of evidence implicates human heart mast cells (HHMCs) in anaphylaxis. These cells have been identified perivascularly, in dose proximity to myocytes and in the arterial intima in human heart tissue. The membrane surface of mast cells from human heart tissue of patients undergoing cardiac transplantation expresses the high affinity receptors for IgE (FcepsilonRI) and C5a receptors. Activation of HHMCs in vitro with anti-IgE or anti-FcepsilonRI induced the release of preformed mediators (histamine, tryptase and chymase) and the de novo synthesis of LTC4 (approximately equal to 18 ng/10(6) cells) and PGD2 (approximately equal to 18 ng/10(6) cells). Complement activation and anaphylatoxin formation occur during anaphylaxis in human. C5a caused rapid release of histamine and tryptase from HHMCs. These cells are activated in vitro by therapeutic (general anaesthetics, protamine, etc.) and diagnostic agents (radio contrast media, etc.) that may cause non-IgE-mediated anaphylactic reactions. Administration of low concentrations of histamine and cysteinyl leukotrienes in subjects undergoing diagnostic catheterization caused significant systemic and coronary haemodynamic effects. Taken together, these results indicate that the human heart can be both the site and the target of anaphylactic reactions.
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May 2004
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