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7. Hyper360 -- a Next Generation Toolset for Immersive Media

Author

Fassold, Hannes, Karakottas, Antonis, Tsatsou, Dorothea, Zarpalas, Dimitrios, Takacs, Barnabas, Fuhrhop, Christian, Manfredi, Angelo, Patz, Nicolas, Tonoli, Simona, and Dulskaia, Iana

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Spherical 360{\deg} video is a novel media format, rapidly becoming adopted in media production and consumption of immersive media. Due to its novelty, there is a lack of tools for producing highly engaging interactive 360{\deg} video for consumption on a multitude of platforms. In this work, we describe the work done so far in the Hyper360 project on tools for mixed 360{\deg} video and 3D content. Furthermore, the first pilots which have been produced with the Hyper360 tools and results of the audience assessment of the produced pilots are presented., Comment: Technical report

Published
2021

8. A critical view on autoantibodies in lupus nephritis: Concrete knowledge based on evidence

Author

Bruschi, Maurizio, Angeletti, Andrea, Prunotto, Marco, Meroni, Pier Luigi, Ghiggeri, Gian Marco, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavalli, Andrea, Scapozza, Leonardo, Patel, Jigar J., Tan, John C., Lo, Ken C., Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Giannese, Domenico, Manfredi, Angelo, Ramirez, Giuseppe A., Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Bui, Federica, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisan, Isabella, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Mescia, Federica, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Ravelli, Angelo, Murtas, Corrado, Candiano, Giovanni, Caridi, Gianluca, La Porta, Edoardo, and Verrina, Enrico

Published
2024
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9. The Hyper360 toolset for enriched 360$^\circ$ video

Author

Fassold, Hannes, Karakottas, Antonis, Tsatsou, Dorothea, Zarpalas, Dimitrios, Takacs, Barnabas, Fuhrhop, Christian, Manfredi, Angelo, Patz, Nicolas, Tonoli, Simona, and Dulskaia, Iana

Subjects
Computer Science - Multimedia
Abstract

360$^\circ$ video is a novel media format, rapidly becoming adopted in media production and consumption as part of todays ongoing virtual reality revolution. Due to its novelty, there is a lack of tools for producing highly engaging 360$^\circ$ video for consumption on a multitude of platforms. In this work, we describe the work done so far in the Hyper360 project on tools for 360$^\circ$ video. Furthermore, the first pilots which have been produced with the Hyper360 tools are presented., Comment: accepted for Collaborative Research and Innovation Projects track at ICME 2020

Published
2020

11. DNA polymorphisms in inflammatory and endocrine signals linked to frailty are also associated with obesity: data from the FRASNET cohort.

Author

Damanti, Sarah, Citterio, Lorena, Zagato, Laura, Brioni, Elena, Magnaghi, Cristiano, Simonini, Marco, De Lorenzo, Rebecca, Ruggiero, Mariapia, Santoro, Simona, Senini, Eleonora, Messina, Marco, Vitali, Giordano, Manunta, Paolo, Manfredi, Angelo Andrea, Lanzani, Chiara, and Querini, Patrizia Rovere

Subjects
BODY composition, SINGLE nucleotide polymorphisms, BLOOD collection, BIOELECTRIC impedance, OLDER people
Abstract

Background: Obesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity. Methods: We aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures. Results: SNPs related to frailty and linked to the renin-angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21-23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults. Conclusions: Frailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies. [ABSTRACT FROM AUTHOR]

Published
2024
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14. #2123 Ageing, renal function and frailty: analysis of the FRASNET study

Author

Lanzani, Chiara Livia, primary, Simonini, Marco, additional, Citterio, Lorena, additional, Zagato, Laura, additional, Brioni, Elena, additional, Damanti, Sarah, additional, Messaggio, Elisabetta, additional, Concas, Maria Pina, additional, Querini, Patrizia Rovere, additional, Manfredi, Angelo, additional, and Manunta, Paolo, additional

Published
2024
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16. Patients with COVID-19: in the dark-NETs of neutrophils

Author

Ackermann, Maximilian, Anders, Hans-Joachim, Bilyy, Rostyslav, Bowlin, Gary L., Daniel, Christoph, De Lorenzo, Rebecca, Egeblad, Mikala, Henneck, Timo, Hidalgo, Andrés, Hoffmann, Markus, Hohberger, Bettina, Kanthi, Yogendra, Kaplan, Mariana J., Knight, Jason S., Knopf, Jasmin, Kolaczkowska, Elzbieta, Kubes, Paul, Leppkes, Moritz, Mahajan, Aparna, Manfredi, Angelo A., Maueröder, Christian, Maugeri, Norma, Mitroulis, Ioannis, Muñoz, Luis E., Narasaraju, Teluguakula, Naschberger, Elisabeth, Neeli, Indira, Ng, Lai Guan, Radic, Marko Z., Ritis, Konstantinos, Rovere-Querini, Patrizia, Schapher, Mirco, Schauer, Christine, Simon, Hans-Uwe, Singh, Jeeshan, Skendros, Panagiotis, Stark, Konstantin, Stürzl, Michael, van der Vlag, Johan, Vandenabeele, Peter, Vitkov, Ljubomir, von Köckritz-Blickwede, Maren, Yanginlar, Cansu, Yousefi, Shida, Zarbock, Alexander, Schett, Georg, and Herrmann, Martin

Published
2021
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18. Inflammatory Markers Predict Blood Neurofilament Light Chain Levels in Acute COVID-19 Patients.

Author

De Lorenzo, Rebecca, Loré, Nicola I., Finardi, Annamaria, Mandelli, Alessandra, Calesella, Federico, Palladini, Mariagrazia, Cirillo, Daniela M., Tresoldi, Cristina, Ciceri, Fabio, Rovere-Querini, Patrizia, Manfredi, Angelo A., Mazza, Mario G., Benedetti, Francesco, and Furlan, Roberto

Subjects
COVID-19 pandemic, COVID-19, CYTOPLASMIC filaments, NERVOUS system, ACUTE diseases
Abstract

Acute coronavirus disease 2019 (COVID-19) is paralleled by a rise in the peripheral levels of neurofilament light chain (NfL), suggesting early nervous system damage. In a cohort of 103 COVID-19 patients, we studied the relationship between the NfL and peripheral inflammatory markers. We found that the NfL levels are significantly predicted by a panel of circulating cytokines/chemokines, including CRP, IL-4, IL-8, IL-9, Eotaxin, and MIP-1ß, which are highly up-regulated during COVID-19 and are associated with clinical outcomes. Our findings show that peripheral cytokines influence the plasma levels of the NfL, suggesting a potential role of the NfL as a marker of neuronal damage associated with COVID-19 inflammation. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Histone‐Specific CD4+ T Cell Plasticity in Active and Quiescent Systemic Lupus Erythematosus.

Author

Ramirez, Giuseppe A., Tassi, Elena, Noviello, Maddalena, Mazzi, Benedetta A., Moroni, Luca, Citterio, Lorena, Zagato, Laura, Tombetti, Enrico, Doglio, Matteo, Baldissera, Elena M., Bozzolo, Enrica P., Bonini, Chiara, Dagna, Lorenzo, and Manfredi, Angelo A.

Subjects
FLOW cytometry, T cells, IMMUNOSUPPRESSIVE agents, CELL physiology, SYSTEMIC lupus erythematosus, DESCRIPTIVE statistics, HISTONES, BIOINFORMATICS, RESEARCH, INDIVIDUALIZED medicine, SEROPREVALENCE, CYTOKINES, DATA analysis software, HLA-B27 antigen, GENOTYPES, BLOOD
Abstract

Objective: The aim of this study was to assess whether circulating histone‐specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE). Methods: Seroprevalence of autoantibodies and HLA‐DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA–peptide autoepitope couples for ex vivo detection of antigen‐specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA‐DRB1*03:01 and/or HLA‐DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission. Results: Histone‐specific CD4+ T cells were selectively detected in patients with SLE. Among patients with a history of anti‐DNA antibodies, 77% had detectable histone‐specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone‐specific regulatory and effector T helper (Th) 1‐, Th2‐, and atypical Th1/Th17 (Th1*)‐polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1‐, Th2‐, and Th1*‐polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone‐specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone‐specific naive T (TN) and terminally differentiated T cells. Conclusion: Histone‐specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Platelet–Leukocyte Interactions

Author

Evangelista, Virgilio, Totani, Licia, Manfredi, Angelo A., Maugeri, Norma, Gresele, Paolo, editor, Kleiman, Neal S., editor, Lopez, José A., editor, and Page, Clive P., editor

Published
2017
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23. To NET or not to NET:current opinions and state of the science regarding the formation of neutrophil extracellular traps

Author

Boeltz, Sebastian, Amini, Poorya, Anders, Hans-Joachim, Andrade, Felipe, Bilyy, Rostyslav, Chatfield, Simon, Cichon, Iwona, Clancy, Danielle M., Desai, Jyaysi, Dumych, Tetiana, Dwivedi, Nishant, Gordon, Rachael Ann, Hahn, Jonas, Hidalgo, Andrés, Hoffmann, Markus H., Kaplan, Mariana J., Knight, Jason S., Kolaczkowska, Elzbieta, Kubes, Paul, Leppkes, Moritz, Manfredi, Angelo A., Martin, Seamus J., Maueröder, Christian, Maugeri, Norma, Mitroulis, Ioannis, Munoz, Luis E., Nakazawa, Daigo, Neeli, Indira, Nizet, Victor, Pieterse, Elmar, Radic, Marko Z, Reinwald, Christiane, Ritis, Konstantinos, Rovere-Querini, Patrizia, Santocki, Michal, Schauer, Christine, Schett, Georg, Shlomchik, Mark Jay, Simon, Hans-Uwe, Skendros, Panagiotis, Stojkov, Darko, Vandenabeele, Peter, Berghe, Tom Vanden, van der Vlag, Johan, Vitkov, Ljubomir, von Köckritz-Blickwede, Maren, Yousefi, Shida, Zarbock, Alexander, and Herrmann, Martin

Published
2019
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26. Choroid Plexus Enlargement In Systemic Lupus Erythematosus: Relationship With Auto-Antibody Status And Neuropsychiatric Involvement (P10-3.016)

Author

Gueye, Mor, primary, Preziosa, Paolo, additional, Ramirez, Giuseppe A., additional, Bozzolo, Enrica, additional, Canti, Valentina, additional, Margoni, Monica, additional, Meani, Alessandro, additional, Rovere-Querini, Patrizia, additional, Manfredi, Angelo, additional, Rocca, Maria, additional, and Filippi, Massimo, additional

Published
2023
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36. Association between Perceived Health-Related Quality of Life and Depression with Frailty in the FRASNET Study

Author

Delli Zotti, Giulia B., primary, Citterio, Lorena, additional, Farinone, Sara, additional, Concas, Maria Pina, additional, Brioni, Elena, additional, Zagato, Laura, additional, Messaggio, Elisabetta, additional, Faienza, Sipontina, additional, Simonini, Marco, additional, Napoli, Alessandra, additional, Di Mattei, Valentina, additional, Rovere-Querini, Patrizia, additional, Sarno, Lucio, additional, Clementi, Emilio, additional, Manfredi, Angelo A., additional, Lanzani, Chiara, additional, and Manunta, Paolo, additional

Published
2022
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38. Evidence for charge-based mimicry in anti dsDNA antibody generation

Author

Bruschi, Maurizio, primary, Angeletti, Andrea, additional, Kajana, Xhuliana, additional, Moroni, Gabriella, additional, Sinico, Renato Alberto, additional, Fredi, Micaela, additional, Vaglio, Augusto, additional, Cavagna, Lorenzo, additional, Pratesi, Federico, additional, Migliorini, Paola, additional, Locatelli, Francesco, additional, Pazzola, Giulia, additional, Pesce, Giampaola, additional, Bagnasco, Marcello, additional, Manfredi, Angelo, additional, Ramirez, Giuseppe Alvise, additional, Esposito, Pasquale, additional, Negrini, Simone, additional, Bui, Federica, additional, Trezzi, Barbara, additional, Emmi, Giacomo, additional, Cavazzana, Ilaria, additional, Binda, Valentina, additional, Fenaroli, Paride, additional, Pisani, Isabella, additional, Montecucco, Carlomaurizio, additional, Santoro, Domenico, additional, Scolari, Francesco, additional, Volpi, Stefano, additional, Mosca, Marta, additional, Tincani, Angela, additional, Candiano, Giovanni, additional, Verrina, Enrico, additional, Franceschini, Franco, additional, Ravelli, Angelo, additional, Prunotto, Marco, additional, Meroni, Pier Luigi, additional, and Ghiggeri, Gian Marco, additional

Published
2022
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39. [New year, new variant: drawing lessons from frail elderly people]

Author

Foligno, Nadia, De Filippo, Marta, De Rosa, Liliana, Bagnati, Costanza, Pomaranzi, Chiara, De Lorenzo, Rebecca, Citterio, Lorena, Messaggio, Elisabetta, Zagato, Laura, Manfredi, Angelo, Rovere-Querini, Patrizia, Manunta, Paolo, Lanzani, Chiara, Foligno, Nadia, De Filippo, Marta, De Rosa, Liliana, Bagnati, Costanza, Pomaranzi, Chiara, De Lorenzo, Rebecca, Citterio, Lorena, Messaggio, Elisabetta, Zagato, Laura, Manfredi, Angelo, Rovere-Querini, Patrizia, Manunta, Paolo, and Lanzani, Chiara

Subjects
SARS-CoV-2, Frail Elderly, frail patients, Humans, COVID-19, FRASNET study, elderly, Pandemics, Personal Protective Equipment, Aged
Abstract

A recent study called FRASNET enrolled on a voluntary basis a cohort on 1240 elderly people. They were either patients of the Nephrology and Dialysis unit at San Raffaele hospital in Milan, guests of care homes, or members of cultural, social and recreational centers for the elderly in the wider Milan area. Demographic, anthropometric and biochemical data were collected, together with information on comorbidities and pharmacological therapies, psychophysical test results and biological samples. After the first wave of the SARS-Cov-2 pandemic, we have interviewed the members of this same cohort to gather information on possible coronavirus infections and evaluate the impact of the pandemic on frail patients. It emerged that the prevalence of SARS-Cov-2 infections was 0.7% within this cohort. This encouraging result seems to confirm the effectiveness of the measures taken at the start of the pandemic, especially social distancing and personal protective equipment.

Published
2022

40. [The FRASNET study: identification of clinical and social factors of renal failure in an elderly population]

Author

Brioni, Elena, Magnaghi, Cristiano, Villa, Giulia, Giannetta, Noemi, Manara, Duilio F, Magni, Giulia, Delli ZOtti, Giulia, Fontana, Simone, Tunesi, Francesca, Zagato, Laura, Lanzani, Chiara, Manfredi, Angelo, Manunta, Paolo, Brioni, Elena, Magnaghi, Cristiano, Villa, Giulia, Giannetta, Noemi, Manara, Duilio F, Magni, Giulia, Delli ZOtti, Giulia, Fontana, Simone, Tunesi, Francesca, Zagato, Laura, Lanzani, Chiara, Manfredi, Angelo, and Manunta, Paolo

Subjects
fraility, sarcopenia, Cross-Sectional Studies, Chronic Kidney Failure, Frailty, Frail Elderly, Humans, Kidney Failure, Chronic, Renal Insufficiency, Chronic, elderly
Abstract

Background. Chronic renal failure is an epidemic in elderly patients. Older population have an increased prevalence of frailty and sarcopenia, associated with a wide range of adverse health outcomes such as falls, hospitalization, disability. Aim. Describe the sociodemographic and clinical variables of an elderly Lombard population and identify predictors of renal insufficiency. Materials and methods. Cross-sectional observational study conducted in hospitals, in recreational centers for the elderly, in the Universities of the Third Age of the provinces of Milan and Monza-Brianza conducted through a convenience sampling of 1250 subjects over the age of 65. Results. The study identified living alone, annual individual income < € 10,000, polypharmacy, sarcopenia and frailty as predictors of chronic kidney failure. The sample has a mean eGFR of 71.74 mL/min/1.73m2 (SD ± 16.56). Older people living alone are more likely to develop CRI (P = 0.031, confidence interval, CI [1.031-1.905]) as well as having an income < € 10,000 (P = 0.002, CI [0.392-0.923]). Taking more than 11 drugs a day increases the probability of having chronic renal failure by 16 times (P = 0.012, CI [1.155-3.16]). Sarcopenia and frailty increase the likelihood of having chronic renal failure (CRI) (P = 0.001, CI [1.198-2.095]). Conclusions. Identifying predictors of chronic kidney failure is a key step in introducing preventive measures and providing better care to the elderly population.

Published
2022

42. Immunomodulatory Effects of Endoscopic Ultrasound-Guided Thermal Ablation in Patients with Pancreatic Ductal Adenocarcinoma.

Author

Testoni, Sabrina Gloria Giulia, Minici, Claudia, Benetti, Elisa, Clemente, Francesca, Boselli, Daniela, Sciorati, Clara, De Monte, Lucia, Petrone, Maria Chiara, Enderle, Markus, Linzenbold, Walter, Protti, Maria Pia, Manfredi, Angelo, De Cobelli, Francesco, Reni, Michele, Falconi, Massimo, Capurso, Gabriele, Arcidiacono, Paolo Giorgio, and Della-Torre, Emanuel

Subjects
PANCREATIC tumors, ADENOCARCINOMA, DISEASE progression, B cells, ENDOSCOPIC ultrasonography, CANCER chemotherapy, IMMUNOMODULATORS, CATHETER ablation, IMMUNE system, RANDOMIZED controlled trials, RESEARCH funding, ABLATION techniques, MONOCYTES
Abstract

Simple Summary: Thermal ablation under endoscopic ultrasound (EUS)-guidance has been investigated in pancreatic ductal adenocarcinoma (PDAC) based on its potential to boost local and systemic anti-tumor immune response. In a recent phase II randomized controlled trial, ablation of borderline resectable (BR) and locally advanced (LA) PDAC using the HybridTherm Probe (HTP) under EUS-guidance in combination with chemotherapy was shown to ameliorate disease progression at 6 months compared to chemotherapy alone. In this work, we aimed to explore the effects of EUS-ablation with HTP on the systemic immune response in patients with BR and LA PDAC. In contrast to chemotherapy, EUS-HTP selectively affected immunological predictors of poor outcome such as serum levels of APRIL/TNFSF13 and inflammatory monocytes, reinforcing its potential use in selected PDAC patients. Immunological consequences of endoscopic ultrasound (EUS)-local thermal ablation (LTA) for pancreatic ductal adenocarcinoma (PDAC) have not been extensively assessed. We aimed to explore EUS-LTA effects on the systemic immune response in PDAC. Peripheral blood was collected from 10 treatment-naïve patients with borderline resectable and locally advanced PDAC, randomly allocated to Nab-paclitaxel plus Gemcitabine chemotherapy (CT-arm, n = 5) or EUS-LTA with HybridTherm Probe plus CT (HTP + CT-arm, n = 5). Twenty healthy donors were included as controls. Flow-cytometry and multiplex assays were used to profile immune cell subsets and measure serum cytokines/chemokines, respectively. At baseline, PDAC patients showed increased circulating monocytes and lower circulating lymphocytes and CD19+ B cells counts compared to healthy controls. After 4 months, CT induced decrease of B regulatory cells, CD4+ cytotoxic T cells and IL-1β. The addition of EUS-HTP to CT selectively decreased the serum levels of APRIL/TNFSF13 as well as T regulatory cells, total, classic and inflammatory monocytes. Serum levels of APRIL/TNFSF13 and total, classic and inflammatory monocytes counts at baseline were associated with worse overall survival. EUS-HTP has the potential to selectively impact on immune cells and cytokines associated with poor outcomes in PDAC. [ABSTRACT FROM AUTHOR]

Published
2023
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45. Evidence for charge-based mimicry in anti dsDNA antibody generation

Author

Bruschi, M, Angeletti, A, Kajana, X, Moroni, G, Sinico, R, Fredi, M, Vaglio, A, Cavagna, L, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Negrini, S, Bui, F, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Verrina, E, Franceschini, F, Ravelli, A, Prunotto, M, Meroni, P, Ghiggeri, G, Bruschi, Maurizio, Angeletti, Andrea, Kajana, Xhuliana, Moroni, Gabriella, Sinico, Renato Alberto, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe Alvise, Esposito, Pasquale, Negrini, Simone, Bui, Federica, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisani, Isabella, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Verrina, Enrico, Franceschini, Franco, Ravelli, Angelo, Prunotto, Marco, Meroni, Pier Luigi, Ghiggeri, Gian Marco, Bruschi, M, Angeletti, A, Kajana, X, Moroni, G, Sinico, R, Fredi, M, Vaglio, A, Cavagna, L, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Negrini, S, Bui, F, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Verrina, E, Franceschini, F, Ravelli, A, Prunotto, M, Meroni, P, Ghiggeri, G, Bruschi, Maurizio, Angeletti, Andrea, Kajana, Xhuliana, Moroni, Gabriella, Sinico, Renato Alberto, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe Alvise, Esposito, Pasquale, Negrini, Simone, Bui, Federica, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisani, Isabella, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Verrina, Enrico, Franceschini, Franco, Ravelli, Angelo, Prunotto, Marco, Meroni, Pier Luigi, and Ghiggeri, Gian Marco

Abstract

Mechanisms for the generation of anti-dsDNA autoantibodies are still not completely elucidated. One theory states that dsDNA interacts for mimicry with antibodies raised versus other antigens but molecular features for mimicry are unknown. Here we show that, at physiological acid-base balance, anti-Annexin A1 binds IgG2 dsDNA in a competitive and dose-dependent way with Annexin A1 and that the competition between the two molecules is null at pH 9. On the other hand, these findings also show that dsDNA and Annexin A1 interact with their respective antibodies on a strictly pH-dependent basis: in both cases, the binding was minimal at pH 4 and maximal at pH9-10. The anionic charge of dsDNA is mainly conferred by the numerous phosphatidic residues. The epitope binding site of Annexin A1 for anti-Annexin A1 IgG2 was here characterized as a string of 34 amino acids at the NH2 terminus, 10 of which are anionic. Circulating levels of anti-dsDNA and anti-Annexin A1 IgG2 antibodies were strongly correlated in patients with systemic lupus erythematosus (n 496) and lupus nephritis (n 425) stratified for age, sex, etc. These results show that dsDNA competes with Annexin A1 for the binding with anti-Annexin A1 IgG2 on a dose and charged mediated base, being able to display an inhibition up to 75%. This study provides the first demonstration that dsDNA may interact with antibodies raised versus other anionic molecules (anti-Annexin A1 IgG2) because of charge mimicry and this interaction may contribute to anti-dsDNA antibodies generation.

Published
2022

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