Article
Chemistry, Medicinal
Juliana P. Vago, Natalia Valdrighi, Esmeralda N. Blaney-Davidson, Daniel L. A. H. Hornikx, Margot Neefjes, Maria E. Barba-Sarasua, Nathalie G. M. Thielen, Martijn H. J. van den Bosch, Peter M. van der Kraan, Marije I. Koenders, Flavio A. Amaral, Fons A. J. van de Loo
Summary: This study investigated the anti-inflammatory effects of Gas6, a TAM receptor ligand, in synovial fibroblasts from osteoarthritis (OA) patients. Gas6 was found to reduce the levels of inflammatory markers, and its effects depended on the activation of the Axl receptor and the induction of SOCS1/3.
Article
Rheumatology
M. Bellan, M. Quaglia, A. Nerviani, D. Mauro, M. Lewis, F. Goegan, A. Gibbin, S. Pagani, L. Salmi, L. Molinari, L. M. Castello, G. C. Avanzi, V Cantaluppi, M. Pirisi, P. P. Sainaghi, C. Pitzalis
Summary: The study found that plasma concentrations of Gas6, sAxl, and sMer are associated with the severity of lupus nephritis in patients with systemic lupus erythematosus. These biomarkers are directly correlated with creatinine and daily proteinuria, and inversely related to creatinine clearance. Additionally, the level of proteinuria is positively correlated with the plasma concentrations of Gas6, sAxl, and sMer.
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Agata Poswiata, Kamila Kozik, Marta Miaczynska, Daria Zdzalik-Bielecka
Summary: This study reveals the coupling between AXL endocytic trafficking and AKT signaling upon GAS6 stimulation, and provides a rationale for pharmacological inhibition of AXL in antiviral therapy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Hyuncheol Jung, Se Young Lee, Seongjoon Lim, Hyeong Ryeol Choi, Yeseong Choi, Minjin Kim, Segi Kim, Yujean Lee, Kyung Ho Han, Won-Suk Chung, Chan Hyuk Kim
Summary: In this study, an engineered protein was developed to induce the engulfment of amyloid-beta (Aβ), leading to improved behavior in Alzheimer's disease mouse models. This protein showed better outcomes compared to conventional antibody therapy, without causing increased inflammation or vascular pathology.
Article
Medicine, General & Internal
Marta Fanlo-Maresma, Beatriz Candas-Estebanez, Virginia Esteve-Luque, Ariadna Padro-Miquel, Francesc Escrihuela-Vidal, Monica Carratini-Moraes, Emili Corbella, Xavier Corbella, Xavier Pinto
Summary: In women with SLE, plasma TG concentrations, GCKR CC homozygosity, and hypertension are independent predictors of carotid atherosclerosis.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Manuela Rizzi, Stelvio Tonello, Davide D'Onghia, Pier Paolo Sainaghi
Summary: Gas6 is a widely expressed protein involved in various biological processes. It serves as the main ligand for TAMs, and its activation plays a crucial role in modulating inflammatory responses and fibrotic evolution. This review focuses on Gas6/TAM axis activation in SARS-CoV-2 infection and highlights the potential therapeutic benefits of targeting Axl, a receptor member of TAMs, in COVID-19 management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Daria Zdzalik-Bielecka, Agata Poswiata, Kamila Kozik, Kamil Jastrzebski, Kay Oliver Schink, Marta Brewinska-Olchowik, Katarzyna Piwocka, Harald Stenmark, Marta Miaczynska
Summary: The study identified an interactome of AXL and its associations with proteins regulating actin dynamics. GAS6-mediated AXL activation triggered actin remodeling and macropinocytosis, promoting the survival of cancer cells under glutamine-deprived conditions. AXL activation by GAS6 drove invasion of cancer cells through actin-driven cytoskeletal rearrangements.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, General & Internal
Ji-Won Kim, Wook-Young Baek, Ju-Yang Jung, Hyoun-Ah Kim, Cheong In Yang, Seung-Ju Kim, Chang-Hee Suh
Summary: This study found that seasonal vitamin D levels are correlated with clinical manifestations and disease activity in lupus patients. Adequate vitamin D levels are important for achieving a low disease activity state in both winter and summer.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biotechnology & Applied Microbiology
Stelvio Tonello, Manuela Rizzi, Erica Matino, Martina Costanzo, Giuseppe Francesco Casciaro, Alessandro Croce, Eleonora Rizzi, Erika Zecca, Anita Pedrinelli, Veronica Vassia, Raffaella Landi, Mattia Bellan, Luigi Mario Castello, Rosalba Minisini, Venkata Ramana Mallela, Davide D'Onghia, Gian Carlo Avanzi, Mario Pirisi, Daniele Lilleri, Pier Paolo Sainaghi
Summary: This study aimed to evaluate whether Gas6, sAxl, and sMerTK could serve as early predictors of disease progression in COVID-19 patients. The study found that higher plasma Gas6 concentrations at hospital admission were associated with worsened clinical conditions, while lower sMerTK concentrations at baseline and after 7 days of hospitalization were associated with a more favorable outcome. Multivariate analysis showed that only baseline Gas6 measurement predicted an adverse prognosis.
Article
Genetics & Heredity
Satish Pasula, Jaanam Gopalakrishnan, Yao Fu, Kandice L. Tessneer, Mandi M. Wiley, Richard C. Pelikan, Jennifer A. Kelly, Patrick M. Gaffney
Summary: This study demonstrates the complex chromatin regulatory network at the TNFAIP3 locus and its role in autoimmune disease pathology. SNPs on this locus can lead to upregulation of certain genes while suppressing TNFAIP3 expression, highlighting the mechanistic potency of this locus in autoimmune diseases.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Francesco Gavelli, Luca Molinari, Marco Baldrighi, Livia Salmi, Filippo Mearelli, Nicola Fiotti, Filippo Patrucco, Chiara Airoldi, Mattia Bellan, Pier Paolo Sainaghi, Salvatore Di Somma, Enrico Lupia, Efrem Colonetti, Maria Lorenza Muiesan, Gianni Biolo, Gian Carlo Avanzi, Luigi Mario Castello
Summary: This study found that measuring the concentration of sMer and Gas6 at the emergency department did not predict mortality, but these biomarkers were associated with acute kidney injury, thrombocytopenia, deranged prothrombin time-international normalized ratio, and sepsis-induced coagulopathy, suggesting a role in predicting sepsis-related organ damage.
Review
Microbiology
Daria Apostolo, Luciana L. Ferreira, Alice Di Tizio, Barbara Ruaro, Filippo Patrucco, Mattia Bellan
Summary: The tyrosine kinase receptors of the TAM family and their ligand Gas6 play a crucial role in innate immunity and inflammatory response. The Gas6/TAM system is involved in the recognition of apoptotic debris by immune cells, which has been exploited by viruses like COVID-19 for cell entry and infection. Understanding the mechanisms underlying COVID-related fibrosis, particularly in the lungs, is still limited, and this review aims to integrate the current knowledge of the Gas6/TAM axis with the pathophysiological mechanisms of COVID-19, focusing on the development of a fibrotic phenotype.
Article
Rheumatology
Lingxiao Xu, Jian Zhao, Qing Sun, Xue Xu, Lei Wang, Ting Liu, Yunjuan Wu, Jingfeng Zhu, Linyu Geng, Yun Deng, Alexander Awgulewitsch, Diane L. Kamen, Jim C. Oates, Prithvi Raj, Edward K. Wakeland, R. Hal Scofield, Joel M. Guthridge, Judith A. James, Bevra H. Hahn, Deborah K. McCurdy, Fang Wang, Miaojia Zhang, Wenfeng Tan, Gary S. Gilkeson, Betty P. Tsao
Summary: This research found two novel SAT1 LOF variants through whole exome sequencing in families with multiple siblings affected by systemic lupus erythematosus (SLE), demonstrating their association with SLE. The study highlights the pathogenic role of dysregulated polyamine catabolism in lupus.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Quentin Moyon, Delphine Sterlin, Makoto Miyara, Francois Anna, Alexis Mathian, Raphael Lhote, Pascale Ghillani-Dalbin, Paul Breillat, Sasi Mudumba, Sophia de Alba, Fleur Cohen-aubart, Julien Haroche, Micheline Pha, Thi Huong Du Boutin, Hedi Chaieb, Pedro Macedo Flores, Pierre Charneau, Guy Gorochov, Zahir Amoura
Summary: This study evaluated disease activity and immune responses in SLE patients following BNT162b2 vaccination. MMF and MTX treatments were found to be associated with reduced antibody response, while anti-spike antibody response was positively correlated with baseline immunoglobulin levels, naive B cell frequencies, and SARS-CoV-2-specific T cell response.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Review
Immunology
Paul Curtiss, Amanda M. Walker, Benjamin F. Chong
Summary: This study reviewed patient cohorts and populations to investigate the progression of cutaneous lupus to systemic lupus. The study found variations in the progression rates between adult and pediatric groups, which were attributed to differences in patient populations, study design, diagnostic criteria, and follow-up time. Risk factors associated with the development of systemic lupus included positive anti-nuclear antibodies, hematologic abnormalities, and a higher number of lupus classification criteria at baseline.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
G. Pires da Rosa, E. Ferreira, B. Sousa-Pinto, P. Bettencourt, G. Espinosa, R. Cervera
Summary: This study analyzed a cohort of patients with laboratory criteria for anti-phospholipid syndrome (APS) but only presenting "non-criteria" clinical manifestations. The patients were compared with definite APS patients. The results showed that these "clinical non-criteria" patients had mainly hematological and neurological involvements, with significant treatment use. Some patients may progress to future systemic lupus erythematosus (SLE).
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Rheumatology
Giuseppe Barilaro, Carlo Della Rocca, Alexandra Esteves, Ricard Cervera, Gerard Espinosa
Summary: This study analyzed the association between the average 'adjusted' Global APS Score (aGAPSS) and the change in Damage Index for APS (DIAPS) in patients with thrombotic and non-thrombotic APS. The results showed that a higher average aGAPSS value was associated with an increase in DIAPS during follow-up, suggesting that the average aGAPSS score can predict the increase in DIAPS.
Article
Cardiac & Cardiovascular Systems
Luis Ortega-Paz, Helena Cristobal, Jose Tomas Ortiz-Perez, Pablo Garcia de Frutos, Guiomar Mendieta, Elena Sandoval, Juan Jose Rodriguez, Emilio Ortega, Ana Garcia-Alvarez, Salvatore Brugaletta, Manel Sabate, Ana Paula Dantas
Summary: In-vitro experiments on myocardial fibroblasts from patients with HFrEF found that Dapagliflozin alone dose-dependently slowed migration of the fibroblasts, and the combination of Dapagliflozin + LCZ696 further reduced migration rate, while Dapagliflozin + spironolactone altered the effects of SGLT2i on biomarkers.
Editorial Material
Medicine, General & Internal
Giuseppe Barilaro, Ricard Cervera
EUROPEAN JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Rheumatology
Mohamed-Yacine Khitri, Alessandra Bartoli, Georgina Maalouf, Alban Deroux, Carlo Salvarani, Giacomo Emmi, Omer Karadag, Gerard Espinosa, Mathilde Leclercq, Gabriele Simonini, Mathieu Vautier, Patrice Cacoub, David Saadoun
Summary: This study evaluated the efficacy of tocilizumab in patients with refractory Behcet disease. The results showed that 83% of patients responded to tocilizumab, with 60% achieving complete response and 23% achieving partial response. Tocilizumab also significantly reduced steroid dosage and the need for concomitant disease-modifying antirheumatic drugs. However, a small number of patients experienced mild to moderate side effects and serious adverse events.
JOURNAL OF RHEUMATOLOGY
(2023)
Article
Medicine, General & Internal
Isaac Pons, Joana Louro, Marta Sitges, Barbara Vidal, Ricard Cervera, Gerard Espinosa
Summary: This study describes the prevalence, clinical and laboratory features, and evolution of heart valve involvement in patients with APS. The results showed that 50% of APS patients had valve involvement, with most of them being female and having arterial hypertension and arterial thrombosis. The valve involvement group had a higher mortality rate.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, General & Internal
Albert Perez-Isidro, Marc Xipell, Arturo Llobell, Noemi De Moner, Gema M. Lledo, Ricard Cervera, Sergio Prieto-Gonzalez, Luis F. Quintana, Gerard Espinosa, Mila Garcia-Ormaechea, Estibaliz Ruiz-Ortiz, Odette Vinas
Summary: This study investigated whether dsDNA antibody-secreting B-cells could be a complementary biomarker for monitoring disease activity and prognosis in SLE patients. The results showed that SLE-ELISpot had the best performance in identifying active patients. High SLE-ELISpot results were associated with haematological involvement and increased risk of disease flare-up, especially renal flare. Combining hypocomplementemia and high SLE-ELISpot results further increased these risks. Therefore, adding SLE-ELISpot to the current follow-up protocol can improve clinicians' personalized care decisions.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Health Care Sciences & Services
Helena Cristobal, Cristina Enjuanes, Montserrat Batlle, Marta Tajes, Begona Campos, Josep Francesch, Pedro Moliner, Marta Farrero, Rut Andrea, Jose Tomas Ortiz-Perez, Albert Morales, Manel Sabate, Josep Comin-Colet, Pablo Garcia de Frutos
Summary: Heart failure (HF) is classified based on left ventricular ejection fraction (EF) into HF with reduced, mildly reduced, and preserved EF. Biomarkers may differ depending on EF type. This study analyzed the levels of soluble form of the AXL receptor tyrosine kinase (sAXL) in HF patients with reduced and preserved EF. The results showed that sAXL levels were a reliable predictor for all-cause and cardiovascular mortality only in the HFpEF cohort.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Dermatology
Bianca Bergamini, Julien Seneschal, Kristin J. Meyers, Frederick Durand, Ewa Haladyj, Gerard Espinosa, Jacob P. Thyssen
Summary: A total of 117 pregnancies with exposure to baricitinib were analyzed, and the clinical outcomes were found to be comparable to other targeted therapies for immune-mediated diseases or general population.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Editorial Material
Rheumatology
Gerard Espinosa, Ricard Cervera
Review
Medicine, General & Internal
Adriana Pane, Camila Milad, Marta Santana-Dominguez, Nuria Banos, Cristina Borras-Novell, Gerard Espinosa, Laura Magnano, Meritxell Nomdedeu, Pedro Juan Moreno-Lozano, Frederic Cofan, Merce Placeres, Rosa Maria Fernandez, Judit Garcia-Villoria, Gloria Garrabou, Irene Vinagre, Laura M. Tanner, Cristina Montserrat-Carbonell, Maria de Tallo Forga-Visa
Summary: Lysinuric protein intolerance (LPI) is a rare metabolic disorder that presents challenges during pregnancy and delivery. This case report highlights the successful natural birth of a woman with LPI, despite various challenges and risks. Collaboration between interdisciplinary teams and careful consideration of risks are crucial in achieving a successful pregnancy and delivery.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Health Care Sciences & Services
Ivan Contreras, Judith Navarro-Otano, Ignasi Rodriguez-Pinto, Amparo Gueemes, Eduarda Alves, Roberto Rios-Garces, Gerard Espinosa, Aida Alejaldre, Aleix Beneyto, Charrise Mary Ramkissoon, Josep Vehi, Ricard Cervera
Summary: This study explores the relationship between the autonomic nervous system and inflammatory pathways in systemic lupus erythematosus patients. The aim is to improve patient outcomes by treating autonomic nervous system dysregulation with noninvasive vagus nerve stimulation. Data on biomarkers, physiological signals, patient outcomes, and quality of life are being collected and analyzed. The results of this study will contribute to the development of patient-tailored vagus nerve stimulation therapies and improve the quality of life for systemic lupus erythematosus patients.
JMIR RESEARCH PROTOCOLS
(2023)