Article
Hematology
Antonella Capozzi, Gloria Riitano, Serena Recalchi, Valeria Manganelli, Roberta Costi, Francesco Saccoliti, Fabio Pulcinelli, Tina Garofalo, Roberta Misasi, Agostina Longo, Roberto Di Santo, Maurizio Sorice
Summary: Anti-phospholipid syndrome (APS) is associated with arterial and venous thrombosis and pregnancy morbidity due to the presence of anti-phospholipid antibodies. This study found that the novel drug RDS3337 can inhibit Heparanase activity, preventing TF expression triggered by anti-beta 2-GPI and reducing platelet aggregation and ATP release. These findings suggest a potential new target for regulating procoagulant proteins in APS.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Immunology
Laura Naranjo, Ljudmila Stojanovich, Aleksandra Djokovic, Laura Andreoli, Angela Tincani, Maria Mslinska, Savino Sciascia, Maria Infantino, Sara Garcinuno, Kinga Kostyra-Grabczak, Mariangela Manfredi, Francesca Regola, Natasa Stanisavljevic, Milomir Milanovic, Jovica Saponjski, Dario Roccatello, Irene Cecchi, Massimo Radin, Maurizio Benucci, Daniel Pleguezuelo, Manuel Serrano, Yehuda Shoenfeld, Antonio Serrano
Summary: The aim of this multicenter, cross-sectional and observational study was to evaluate the association between the presence of circulating immune complexes (CIC) formed by beta-2-glycoprotein-I (B2GP1) and anti-B2GP1 antibodies (B2-CIC) and clinical manifestations in patients with antiphospholipid syndrome (APS). The results showed that patients with thrombotic events and positive for B2-CIC had lower platelet count and complement levels, suggesting a greater degree of platelet activation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Suresh Kumar, Mathivanan Chinnaraj, William Planer, Xiaobing Zuo, Paolo Macor, Francesco Tedesco, Nicola Pozzi
Summary: The study reveals the distinct roles of the two disulfide bonds, C32-C60 and C288-C326, in regulating the structure and function of β(2)GPI. While the C32-C60 bond plays a structural role, the C288-C326 bond functions as an allosteric switch controlling the protein's physiological functions in a redox-dependent manner.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Immunology
Savino Sciascia, Rory Bloch, Tyler O'Malley, Anja Kammesheidt, Roberta Vezza Alexander
Summary: High titers of aPL often remain positive, allowing for earlier diagnosis and risk assessment at the initial screening. Low titers may require retesting. There is a high correlation between aCL and aB2GP1 measured using two different technologies. The correlation between PC4d and aPL is low to moderate, suggesting a possible additional value in evaluating the association with thrombosis in autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lijiang Shen, Andrea Wong, Satoru Oneda, Brian R. Curtis, Joe Schroeder, Tom Zanardi, Jeffery A. Engelhardt, Scott P. Henry, Padmakumar Narayanan
Summary: The use of 2'-O-methoxyethyl antisense oligonucleotide (2'-MOE ASO) in Asian-sourced cynomolgus monkeys leads to severe thrombocytopenia (TCP) with a low incidence. Further studies with Mauritian-sourced cynomolgus monkeys indicate that TCP is more likely to occur in these monkeys and is associated with increased platelet clearance due to complement deposition. There is also a correlation between serum antiglycoprotein (GP) IIb/IIIa immunoglobulin G (IgG) and platelet reduction, as well as increased levels of total serum IgM and anti-platelet IgM in both sources of monkeys.
NUCLEIC ACID THERAPEUTICS
(2023)
Review
Immunology
Adele Couvidou, Gabriel Rojas-Jimenez, Arnaud Dupuis, Blandine Maitre
Summary: Patients with hematological disorders and severe thrombocytopenia often face the challenge of platelet transfusion refractoriness, a condition where recipient alloantibodies rapidly remove transfused platelets. This can lead to therapeutic and prophylactic transfusion failure and increase the risk of major bleeding. This review explores the underlying mechanisms and characteristics of the antibodies involved, and discusses potential future therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Li Wu, Xuhui Fang, Fangting Lu, Yu Zhang, Yanshi Wang, Joanne Kwak-Kim
Summary: This study aimed to evaluate the effects of anticardiolipin (aCL) and/or anti-beta 2-glycoprotein-I (a beta 2GPI) antibodies, known as antiphospholipid antibodies (aPL), on in vitro fertilization (IVF) outcomes. The results showed that infertile women with aPL had worse outcomes in terms of oocyte quality, embryo quality, and implantation capacity. Imbalanced T cell subset ratios and elevated levels of certain cytokines were noticed in these women compared to controls.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Aymric Kisserli, Nathalie Schneider, Sandra Audonnet, Thierry Tabary, Antoine Goury, Joel Cousson, Rachid Mahmoudi, Firouze Bani-Sadr, Lukshe Kanagaratnam, Damien Jolly, Jacques H. M. Cohen
Summary: The study observed decreased CR1 density and increased C4d deposits on erythrocytes of COVID-19 patients, which were associated with disease severity. This suggests that complement activation and inflammation play important roles in the pathophysiology of COVID-19.
Article
Medicine, General & Internal
Martina Frodlund, Tomas Walhelm, Charlotte Dahle, Christopher Sjowall
Summary: In patients with recent-onset SLE, a substantial percentage tested positive for at least one aPL isotype or the lupus anticoagulant test over time. Levels of all six aPL isotypes numerically decreased from inclusion to last follow-up. The presence of IgG aCL was significantly associated with myocardial infarction and miscarriage, while IgG/IgA anti-beta 2GPI was linked to miscarriage.
FRONTIERS IN MEDICINE
(2021)
Article
Neurosciences
Fadi Hassan, Mohammad E. Naffaa, Amir Saab, Chaim Putterman
Summary: Cognitive impairment is a frequent issue in APS patients and aPL carriers, but it is not well-studied compared to other manifestations of the condition. The prevalence of cognitive impairment in these patients has not been accurately determined due to inconsistent tools used, small sample sizes, and variability in antibody measurements. Higher numbers of aPLs and specific antibody loads increase the risk of cognitive impairment. Inflammation-related pathways may also play a role in the development of cognitive impairment in APS. Anti-coagulant and anti-thrombotic medications are the main treatments for APS, and they have shown some positive effects in reversing cognitive impairment, but more evidence is needed regarding their efficacy and safety for this specific condition.
Review
Hematology
Sigbjorn Berentsen
Summary: Significant progress has been made in the treatment of CAD in recent decades, with recommendations mainly based on nonrandomized trials and personal experience due to the lack of comparative trials. Individualized treatment options tailored to patients' symptoms and disease characteristics are crucial to avoid ineffective therapies.
Article
Immunology
Natalia Egri, Chelsea Bentow, Laura Rubio, Gary L. Norman, Susana Lopez-Sanudo, Michael Mahler, Albert Perez-Isidro, Ricard Cervera, Odette Vinas, Gerard Espinosa, Estibaliz Ruiz-Ortiz
Summary: The study found that persistently positive results for aPS/PT IgG antibodies were significantly associated with APS classification, thrombosis, triple aPL positivity, LA positive result, and the Global APS Score (GAPSS) > than 9 points, but not with pregnancy morbidity and SLE.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Gabor Szabo, Ildiko Beke Debreceni, Tunde Tarr, Pal Soltesz, Bjarne Osterud, Janos Kappelmayer
Summary: Anti-beta(2)GPI autoantibodies exert multi-faceted effects in both normal and thrombophilic plasmas, prolonging Lag Time and increasing Peak Thrombin. The prolonging effect is more remarkable in plasma with inherited thrombophilic mutations.
THROMBOSIS RESEARCH
(2021)
Article
Immunology
Freda H. Passam, Gang Chen, Vivien M. Chen, Miao Qi, Steven A. Krilis, Bill Giannakopoulos
Summary: This study found that ss2GPI deficient mice have enhanced thrombus formation compared to wild type mice, and the antithrombotic function of ss2GPI is mainly dependent on its fifth domain.
JOURNAL OF AUTOIMMUNITY
(2022)
Article
Biochemistry & Molecular Biology
Kenji Tanimura, Shigeru Saito, Sayaka Tsuda, Yosuke Ono, Hajime Ota, Shinichiro Wada, Masashi Deguchi, Mikiya Nakatsuka, Takeshi Nagamatsu, Tomoyuki Fujii, Gen Kobashi, Hisashi Arase, Hideto Yamada
Summary: The anti-beta 2-glycoprotein I/HLA-DR antibody is associated with antiphospholipid syndrome and recurrent pregnancy loss. This study demonstrates that the antibody is significantly associated with adverse obstetric outcomes and recurrent pregnancy loss.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Rheumatology
Xavier Bossuyt, Walter Fierz, Pier Luigi Meroni
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Review
Pharmacology & Pharmacy
Silvia Cavalli, Paola Adele Lonati, Maria Gerosa, Roberto Caporali, Rolando Cimaz, Cecilia Beatrice Chighizola
Summary: The complement system has a significant role in various rheumatologic conditions, including rheumatoid arthritis, psoriatic arthritis, Sjogren syndrome, systemic sclerosis, vasculitides, and dermatomyositis. Complement deposition is associated with disease severity, and serum complement levels may serve as potential markers for evaluating disease activity. In pregnancy, the complement system also plays a crucial role, and alterations in complement levels may be associated with pregnancy complications.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Rheumatology
Paola Adele Lonati, Caterina Bodio, Mariangela Scavone, Giuliana Martini, Elisa Pesce, Alessandra Bandera, Andrea Lombardi, Maria Gerosa, Franco Franceschini, Angela Tincani, Gianmarco Podda, Sergio Abrignani, Renata Grifantini, Marco Cattaneo, Maria Orietta Borghi, Pier Luigi Meroni
Summary: The study found that COVID-19 vaccination does not affect the production of anti-PF4 antibodies and their ability to cause platelet activation in aPL-positive patients.
Article
Oncology
Davide Saronni, Germano Gaudenzi, Alessandra Dicitore, Silvia Carra, Maria Celeste Cantone, Maria Orietta Borghi, Andrea Barbieri, Luca Mignani, Leo J. Hofland, Luca Persani, Giovanni Vitale
Summary: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that originates from the parafollicular C cells of the thyroid gland. This preclinical study aimed to evaluate the efficacy of three tyrosine-kinase inhibitors (TKIs), SU5402, sulfatinib, and SPP86, for the treatment of MTC. In vitro experiments were conducted using two human MTC cell lines, and in vivo experiments were performed using xenografts of MTC cells in zebrafish embryos. The results showed that these TKIs reduced cell viability and induced apoptosis in MTC cells. Furthermore, they inhibited cell migration and angiogenesis in zebrafish embryos. These findings suggest that targeting the FGFR and VEGFR signaling pathways may be a potential alternative therapy for MTC.
Article
Immunology
Pier Luigi Meroni, Stefania Croci, Paola Adele Lonati, Francesca Pregnolato, Lucia Spaggiari, Giulia Besutti, Martina Bonacini, Ilaria Ferrigno, Alessandro Rossi, Geir Hetland, Ivana Hollan, Massimo Cugno, Francesco Tedesco, Maria Orietta Borghi, Carlo Salvarani
Summary: COVID-19 can cause a multi-organ disease with hyperinflammation and prothrombotic response. The activation of complement is associated with disease severity and outcome.
AUTOIMMUNITY REVIEWS
(2023)
Letter
Hematology
Bianca Clerici, Mariangela Scavone, Simone Birocchi, Chiara Aloise, Benedetta Peroni, Alessandra Negrini, Claudia Ghali, Giovanni Casazza, Gian Marco Podda
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Letter
Cell Biology
Mariangela Scavone, Gian Marco Podda, Armando Tripodi, Marco Cattaneo
Article
Hematology
Marta Brambilla, Paola Canzano, Patrizia Della Valle, Alessia Becchetti, Maria Conti, Mariangela Alberti, Arianna Galotta, Maria Luisa Biondi, Paola Adele Lonati, Fabrizio Veglia, Alice Bonomi, Nicola Cosentino, Pier Luigi Meroni, Gian Vincenzo Zuccotti, Armando D'Angelo, Marina Camera
Summary: This study evaluated the impact of four COVID-19 vaccines on platelet activation, coagulation, and inflammation. It found that vaccination did not induce platelet activation and microvesicle release. Although there were minor changes in clotting activation and endothelial function, these could potentially explain the rare venous thromboembolic complications of COVID-19 vaccination at a population level.
THROMBOSIS RESEARCH
(2023)
Article
Medicine, General & Internal
Roberta E. Gualtierotti, Sharon Fox, Fernanda Da Silva Lameira, Andrea Giachi, Luca Valenti, Maria Orietta Borghi, Pier Luigi Meroni, Massimo Cugno, Flora Peyvandi
Summary: Nailfold videocapillaroscopic alterations were observed in COVID-19 patients, and these alterations were correlated with biomarkers of inflammation and endothelial perturbation. Nailfold histopathology analysis revealed microvascular damage and microthrombi in some cases. These findings suggest the possibility of non-invasively demonstrating microangiopathy in COVID-19.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Cardiac & Cardiovascular Systems
Bianca Clerici, Marco Cattaneo
Summary: Aspirin irreversibly inhibits platelet function by inhibiting the synthesis of TxA2. Although widely used at low doses for cardiovascular prevention, chronic treatment with aspirin can lead to gastrointestinal discomfort, mucosal erosions/ulcerations, and bleeding. Enteric-coated (EC) aspirin, the most commonly used formulation, is less effective than plain aspirin in inhibiting TxA2 production, especially in individuals with high body weight. It causes fewer erosions in the stomach but can still cause mucosal erosions in the small intestine. Several studies have shown that EC aspirin and buffered aspirin do not significantly reduce the incidence of clinically relevant gastrointestinal ulceration and bleeding. Plain aspirin should be the preferred formulation for cardiovascular prevention due to its favorable pharmacological profile.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2023)
Article
Hematology
Marta Brambilla, Alessia Becchetti, Gian Enrico Rovati, Nicola Cosentino, Maria Conti, Paola Canzano, Peter L. A. Giesen, Alessia Loffreda, Alice Bonomi, Marco Cattaneo, Erica De Candia, Gian Marco Podda, Daniela Trabattoni, Pablo Jose Werba, Jeness Campodonico, Christian Pinna, Giancarlo Marenzi, Elena Tremoli, Marina Camera
Summary: ADP-induced platelet activation leads to the expression of tissue factor (TF) on the cell surface. The study demonstrates that P2Y(12) receptors play a role in regulating TF expression, and P2Y(12) antagonists can reduce the percentage of TF-positive platelets. Assessment of TF-positive platelets can be used to identify patients with residual platelet reactivity.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria Pia Adorni, Bianca Papotti, Maria Orietta Borghi, Elena Raschi, Francesca Zimetti, Franco Bernini, Pier Luigi Meroni, Nicoletta Ronda
Summary: This study investigates the direct effects of tofacitinib on macrophage cholesterol metabolism, finding that it can increase cholesterol efflux, decrease cholesterol uptake and synthesis, and have a favorable impact on macrophage cholesterol metabolism. These findings are important for understanding the impact of tofacitinib on cardiovascular risk.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)