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1. Serum profiling identifies CCL8, CXCL13, and IL-1RA as markers of active disease in patients with systemic lupus erythematosus

Author

Julius Lindblom, Lorenzo Beretta, Maria Orietta Borghi, PRECISESADS Clinical Consortium, Marta E. Alarcón-Riquelme, Ioannis Parodis, Barbara Vigone, Jacques-Olivier Pers, Alain Saraux, Valérie Devauchelle-Pensec, Divi Cornec, Sandrine Jousse-Joulin, Bernard Lauwerys, Julie Ducreux, Anne-Lise Maudoux, Carlos Vasconcelos, Ana Tavares, Esmeralda Neves, Raquel Faria, Mariana Brandão, Ana Campar, António Marinho, Farinha Fátima, Isabel Almeida, Angel Gonzalez-Gay Mantecón, Ricardo Blanco Alonso, Alfonso Corrales Martínez, Ricard Cervera, Ignasi Rodríguez-Pintó, Gerard Espinosa, Rik Lories, Ellen De Langhe, Nicolas Hunzelmann, Doreen Belz, Torsten Witte, Niklas Baerlecken, Georg Stummvoll, Michael Zauner, Michaela Lehner, Eduardo Collantes, Rafaela Ortega-Castro, MaAngeles Aguirre-Zamorano, Alejandro Escudero-Contreras, MaCarmen Castro-Villegas, Norberto Ortego, María Concepción Fernández Roldán, Enrique Raya, Inmaculada Jiménez Moleón, Enrique de Ramon, Isabel Díaz Quintero, Pier Luigi Meroni, Maria Gerosa, Tommaso Schioppo, Carolina Artusi, Carlo Chizzolini, Aleksandra Zuber, Donatienne Wynar, Laszló Kovács, Attila Balog, Magdolna Deák, Márta Bocskai, Sonja Dulic, Gabriella Kádár, Falk Hiepe, Velia Gerl, Silvia Thiel, Manuel Rodriguez Maresca, Antonio López-Berrio, Rocío Aguilar-Quesada, and Héctor Navarro-Linares.

Subjects
autoimmunity, systemic lupus erythematosus, antiphospholipid syndrome, diagnosis, biomarkers, cytokines, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionSystemic lupus erythematosus (SLE) is a clinically heterogeneous disease that presents a challenge for clinicians. To identify potential biomarkers for diagnosis and disease activity in SLE, we investigated a selected yet broad panel of cytokines and autoantibodies in patients with SLE, healthy controls (HC), and patients with other autoimmune diseases (AIDs).MethodsSerum samples from 422 SLE patients, 546 HC, and 1223 other AIDs were analysed within the frame of the European PRECISESADS project (NTC02890121). Cytokine levels were determined using Luminex panels, and autoantibodies using different immunoassays.ResultsOf the 83 cytokines analysed, 29 differed significantly between patients with SLE and HC. Specifically, CCL8, CXCL13, and IL-1RA levels were elevated in patients with active, but not inactive, SLE versus HC, as well as in patients with SLE versus other AIDs. The levels of these cytokines also correlated with SLE Disease Activity Index 2000 (SLEDAI-2K) scores, among five other cytokines. Overall, the occurrence of autoantibodies was similar across SLEDAI-2K organ domains, and the correlations between autoantibodies and activity in different organ domains were weak.DiscussionOur findings suggest that, upon validation, CCL8, CXCL13, and IL-1RA could serve as promising serum biomarkers of activity in SLE.

Published
2023
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3. Interferon and B-cell Signatures Inform Precision Medicine in Lupus Nephritis

Author

Beretta, Lorenzo, Vigone, Barbara, Pers, Jacques-Olivier, Saraux, Alain, Devauchelle-Pensec, Valérie, Cornec, Divi, Jousse-Joulin, Sandrine, Lauwerys, Bernard, Ducreux, Julie, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Neves, Esmeralda, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Angel, Alonso, Ricardo Blanco, Martínez, Alfonso Corrales, Cervera, Ricard, Rodríguez-Pintó, Ignasi, Espinosa, Gerard, Lories, Rik, De Langhe, Ellen, Hunzelmann, Nicolas, Belz, Doreen, Witte, Torsten, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Aguirre-Zamorano, Ma Angeles, Escudero-Contreras, Alejandro, Castro-Villegas, Ma Carmen, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Moleón, Inmaculada Jiménez, de Ramon, Enrique, Quintero, Isabel Díaz, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Chizzolini, Carlo, Zuber, Aleksandra, Wynar, Donatienne, Kovács, Laszló, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Maresca, Manuel Rodriguez, López-Berrio, Antonio, Aguilar-Quesada, Rocío, Navarro-Linares, Héctor, Parodis, Ioannis, Lindblom, Julius, Toro-Domínguez, Daniel, Borghi, Maria O., Castillo, Jessica, Carnero-Montoro, Elena, Enman, Yvonne, Mohan, Chandra, Alarcón-Riquelme, Marta E., Barturen, Guillermo, and Nikolopoulos, Dionysis

Published
2024
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4. Santa Catarina’s Tiles: An Artisanal Heritage to Preserve. Manufacturing Process and Characteristics

Author

Oliveira, Miguel, Gonçalves, Marta Marçal, da Silva, Elisa, Farinha, Fátima, Rocha, Elisabete, Howlett, Robert J., Series Editor, Littlewood, John, Series Editor, Jain, Lakhmi C., Series Editor, Semião, Jorge Filipe Leal Costa, editor, Sousa, Nelson Manuel Santos, editor, da Cruz, Rui Mariano Sousa, editor, and Prates, Gonçalo Nuno Delgado, editor

Published
2023
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5. Technical and Sustainability Analysis of Construction Processes and Covering Systems for Outdoor Swimming Pools

Author

Oliveira, Miguel José, Farinha, Fátima, Marín-García, David, Muniz, Elbes, Howlett, Robert J., Series Editor, Littlewood, John, Series Editor, Jain, Lakhmi C., Series Editor, Semião, Jorge Filipe Leal Costa, editor, Sousa, Nelson Manuel Santos, editor, da Cruz, Rui Mariano Sousa, editor, and Prates, Gonçalo Nuno Delgado, editor

Published
2023
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8. Sustainability Challenges in Outdoor Swimming Pools

Author

Oliveira, Miguel José, Farinha, Fátima, Inverno, Armando, Monteiro, Jânio, Cabrita, Cristiano, Venturinha, Adelino, di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Bienvenido-Huertas, David, editor, and Moyano-Campos, Juan, editor

Published
2022
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11. Analysis of the Regulations that Affect Energy Efficiency with Respect to Consumption of HVAC System for Residential Buildings in Southern Spain and Portugal

Author

Marín-García, David, Bienvenido-Huertas, David, Nieto-Julián, Enrique, Moyano Campos, Juan José, Oliveira, Miguel José, Farinha, Fátima, Monteiro, Jânio, editor, João Silva, António, editor, Mortal, António, editor, Aníbal, Jaime, editor, Moreira da Silva, Manuela, editor, Oliveira, Miguel, editor, and Sousa, Nelson, editor

Published
2020
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12. Psychological impact of life events in systemic lupus erythematosus patients – Differences between flares and remission.

Author

Faria, Raquel, Guimarães de Oliveira, Daniel, Alves, Rute, Farinha, Fátima, Pinho Costa, Paulo, Vasconcelos, Carlos, and Figueiredo-Braga, Margarida

Subjects
PERCEIVED Stress Scale, PSYCHOLOGICAL factors, SYMPTOMS, WOMEN patients, ANXIETY disorders, PSYCHOMETRICS
Abstract

Background: Stress has been linked to worsening symptoms and increased disease activity in patients with Systemic lupus erythematosus (SLE). Life-events are individual stress points, and there is conflicting evidence regarding their role in SLE activity and disease perception. Methods: Adult SLE patients were recruited for the study. Clinical and laboratory features of SLE were recorded, and previous diagnosis of anxiety or depression were retrieved from patients' electronic charts. Flares were defined by the Systemic Lupus Erythematosus Disease Activity (SLEDAI) flare Index, and flares during the previous year were documented. During a routine visit, they completed validated Portuguese translations of the 10-item Perceived Stress Scale (PSS-10), Hospital Anxiety and Depression Scale (HADS) and Life Experience Survey (LES) for the previous year. Results: A total of 47 female SLE patients were recruited. Ten patients (21.3%) had experienced recent flares. Patients with recent flares reported fewer life events, with lower positive, negative, and total weightings sums compared to those without recent flares. Although 42.2% of patients perceived pathological levels of stress in the previous month, 48.9% had anxiety symptoms, and 34% were at high risk for an anxiety disorder, these psychometric measures did not differ significantly between the recent flare and no-flare groups. Conclusions: There is a high prevalence of pathological levels of stress among SLE patients. SLE patients with recent flares report less psychological impact from life events, both positive and negative, independent of other psychological or pharmacological factors. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Interferon and B-cell Signatures Inform Precision Medicine in Lupus Nephritis

Author

Parodis, Ioannis, primary, Lindblom, Julius, additional, Toro-Domínguez, Daniel, additional, Beretta, Lorenzo, additional, Borghi, Maria O., additional, Castillo, Jessica, additional, Carnero-Montoro, Elena, additional, Enman, Yvonne, additional, Mohan, Chandra, additional, Alarcón-Riquelme, Marta E., additional, Barturen, Guillermo, additional, Nikolopoulos, Dionysis, additional, Vigone, Barbara, additional, Pers, Jacques-Olivier, additional, Saraux, Alain, additional, Devauchelle-Pensec, Valérie, additional, Cornec, Divi, additional, Jousse-Joulin, Sandrine, additional, Lauwerys, Bernard, additional, Ducreux, Julie, additional, Maudoux, Anne-Lise, additional, Vasconcelos, Carlos, additional, Tavares, Ana, additional, Neves, Esmeralda, additional, Faria, Raquel, additional, Brandão, Mariana, additional, Campar, Ana, additional, Marinho, António, additional, Farinha, Fátima, additional, Almeida, Isabel, additional, Gonzalez-Gay Mantecón, Miguel Angel, additional, Alonso, Ricardo Blanco, additional, Martínez, Alfonso Corrales, additional, Cervera, Ricard, additional, Rodríguez-Pintó, Ignasi, additional, Espinosa, Gerard, additional, Lories, Rik, additional, De Langhe, Ellen, additional, Hunzelmann, Nicolas, additional, Belz, Doreen, additional, Witte, Torsten, additional, Baerlecken, Niklas, additional, Stummvoll, Georg, additional, Zauner, Michael, additional, Lehner, Michaela, additional, Collantes, Eduardo, additional, Ortega-Castro, Rafaela, additional, Aguirre-Zamorano, Ma Angeles, additional, Escudero-Contreras, Alejandro, additional, Castro-Villegas, Ma Carmen, additional, Ortego, Norberto, additional, Fernández Roldán, María Concepción, additional, Raya, Enrique, additional, Moleón, Inmaculada Jiménez, additional, de Ramon, Enrique, additional, Quintero, Isabel Díaz, additional, Meroni, Pier Luigi, additional, Gerosa, Maria, additional, Schioppo, Tommaso, additional, Artusi, Carolina, additional, Chizzolini, Carlo, additional, Zuber, Aleksandra, additional, Wynar, Donatienne, additional, Kovács, Laszló, additional, Balog, Attila, additional, Deák, Magdolna, additional, Bocskai, Márta, additional, Dulic, Sonja, additional, Kádár, Gabriella, additional, Hiepe, Falk, additional, Gerl, Velia, additional, Thiel, Silvia, additional, Maresca, Manuel Rodriguez, additional, López-Berrio, Antonio, additional, Aguilar-Quesada, Rocío, additional, and Navarro-Linares, Héctor, additional

Published
2024
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17. Case Studies on Energy Retrofitting

Author

Farinha, Fátima, Cristo, Eurídice, Mortal, António, editor, Aníbal, Jaime, editor, Monteiro, Jânio, editor, Sequeira, Cláudia, editor, Semião, Jorge, editor, Moreira da Silva, Manuela, editor, and Oliveira, Miguel, editor

Published
2018
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25. Dolor y articulación de la muñeca en la artritis reumatoide: El impacto en la capacidad funcional

Author

Seixas, Diana, Farinha, Fátima, Fonte, Marcos Pacheco da, Laranjeira, Manuel, and Rua, Marília

Subjects
medidas de resultados relatados pelos doentes, patient reported outcome measures, arthritis, rheumatoid, doenças autoimunes, autoimmune diseases, artritis, reumatoide, enfermidades autoinmunes, artrite reumatoide, medidas de resultado informadas por el pacient
Abstract

Background: Rheumatoid arthritis (RA) is a chronic, autoimmune, and inflammatory disease. Symptoms include polyarthritis, chronic pain, and difficulty in joint mobilization, which lead to functional disability in patients. Objectives: To assess the influence of wrist joint mobility and pain on the functional capacity of patients with RA. Methodology: Quantitative, descriptive, and correlational study in a sample of 105 patients. Health Assessment Questionnaire - Disability Index (HAQ-DI) and Visual Analog Pain Scale (VAS) were applied, and the wrist joint range of motion was measured with a goniometer. Results: Joint wrist mobility is representative of functionality (p < 0.05). However, wrist joint extension and flexion do not directly influence pain (p > 0.05). Pain was observed to impact the functional capacity in patients (p = 0.010). Conclusion: Joint wrist mobility and pain affect the daily activities of patients with RA, expressed through the functional capacity for health assessment., Marco contextual: Artritis reumatoide (AR), una enfermedad autoinmune, inflamatoria y crónica. Se caracteriza por la poliartritis, el dolor crónico y la dificultad para movilizar las articulaciones, lo que provoca la incapacidad funcional de los pacientes. Objetivos: Evaluar la influencia de la movilidad articular de la muñeca y el dolor en la capacidad funcional de los pacientes con AR. Metodología: Estudio cuantitativo, descriptivo y correlacional, compuesto por una muestra de 105 pacientes, en el que se aplicó el Índice de Discapacidad - Cuestionario de Evaluación de la Salud (HAQ-DI); la Escala Visual Analógica del Dolor (EVA) y la medición de la amplitud articular de la muñeca, con un goniómetro. Resultados: La movilidad articular de la muñeca es representativa en la funcionalidad (p < 0,05), sin embargo, la extensión y la flexión no influyen directamente en el dolor (p > 0,05). Se observó que el dolor tiene un impacto en la capacidad funcional de los pacientes (p = 0,010). Conclusión: La movilidad articular de la muñeca y el dolor afectan las actividades diarias de los pacientes con AR, expresadas a través de la capacidad funcional de evaluación de la salud., Enquadramento: Artrite reumatoide (AR), doença autoimune, inflamatória e crónica. Caracteriza-se por poliartrite, dor crónica e dificuldade em mobilizar as articulações, que levam à incapacidade funcional dos doentes. Objetivos: Avaliar a influência da mobilidade articular do punho e da dor, na capacidade funcional de doentes com AR. Metodologia: Estudo quantitativo, descritivo e correlacional, constituído por uma amostra de 105 doentes, com aplicação do Índice de Incapacidade - Questionário Avaliação de Saúde (HAQ-DI); Escala Visual Analógica da Dor (EVA) e medição da amplitude articular do punho, com goniómetro. Resultados: A mobilidade articular do punho é representativa na funcionalidade (p < 0,05), no entanto, a sua extensão e flexão, não influenciam diretamente a dor (p > 0,05). Observou-se que a dor é impactante na capacidade funcional dos doentes (p = 0,010). Conclusão: A mobilidade articular do punho e a dor afetam as atividades diárias dos doentes com AR, expressas através da capacidade funcional de avaliação de saúde.

Published
2022

29. Biologics Drugs in Behçet’s Disease: A Single Centre Experience

Author

Pinto,Luísa Serpa, Pires,Sara Xavier, Carvalheiras,Graziela, Campar,Ana, Marinho,António, Farinha,Fátima, Vasconcelos,Carlos, and Correia,João Araújo

Subjects
Treatment Outcome, Behcet Syndrome/drug therapy, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Biological Products/therapeutic use
Abstract

Introduction: Behçet´s disease (BD) is a systemic vasculitis of unknown cause. Several cytokines, such as tumor necrosis factor-alpha (TNF-α), appear to play a substantial role. Therefore, biologics such as anti-TNF-α agents are rising to control severe or refractory BD´s manifestations. We aimed to describe the biological therapy´s outcomes in BD patients. Methods: A longitudinal, prospective, unicentric cohort study with patients followed in a specialized outpatient clinic. We collected data regarding BD´s manifestations, treatments, and outcomes during follow-up. Results: Our cohort includes 243 patients, of whom 31% were male. During follow-up, 20 patients (8%) were treated with biological drugs. Patients who received biological therapies were younger (p = 0.030), had less frequently genital aphthosis (p = 0.009), and more frequently erythema nodosum (p = 0.009), polyarthritis (p = 0.002), spondyloarthritis (p = 0.024), retinal vasculitis (p = 0.011) and gastrointestinal manifestations (p = 0.024), namely gastroduodenal ulcer (p = 0.035), digestive bleeding from ulcers (p = 0.002), and bowel perforation (p = 0.004). Anti-TNF-α agents were used in all of these patients, most frequently infliximab. Patients started biologicals after classical immunosuppressors failure, and most went into remission (93%). Three patients developed tuberculosis during treatment, regardless of regular screening tests. It was possible to stop biological therapy in five patients, so far, without recurrence, with 33 months of mean follow-up time after suspension. Discussion: Anti-TNF-α agents are highly effective for refractory BD´s manifestations, although they are not innocuous. Little is known about the optimal duration of these therapies, regarding when and how to stop these drugs. This issue is essential not only to avoid relapses but also to reduce therapy side-effects., Medicina Interna, Vol. 28 N.º 4 (2021): Outubro / Dezembro

Published
2021

30. A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome

Author

Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Christophe, Jamin, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valérie, Boudjeniba, Cheïma, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodríguez-Pintó, Ignasi, de Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovács, László, Witte, Torsten, Bettacchioli, Eléonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Borghi, Maria Orietta, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickaël, Moingeon, Philippe, Alarcón-Riquelme, Marta, Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Angel, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Aguirre-Zamorano, Ma Angeles, Escudero-Contreras, Alejandro, Castro-Villegas, Ma Carmen, Jiménez Gómez, Yolanda, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Jiménez Moleón, Inmaculada, de Ramon, Enrique, Díaz Quintero, Isabel, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Zuber, Aleksandra, Wynar, Donatienne, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Thiel, Silvia, Rodriguez Maresca, Manuel, López-Berrio, Antonio, Aguilar-Quesada, Rocío, Navarro-Linares, Héctor, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcón Riquelme, Marta, Gomes Anjos, Tania, Marañón, Concepción, Le Lann, Lucas, Simon, Quentin, Rouvière, Bénédicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Gerl, Velia, Khodadadi, Laleh, Cheng, Qingyu, de Groof, Aurélie, Ducreux, Julie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Neves, Esmeralda, Rao, Sambasiva, Jouve, Pierre-Emmanuel, Institut de Recherches Internationales Servier [Suresnes] (IRIS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre for Genomics and Oncological Reearch (GENYO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Maggiore Hospital, IRCCS Foundation, Milano, Department of Pathology and Immunology [Geneva, Switzerland], Université de Genève = University of Geneva (UNIGE), University of Szeged [Szeged], Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Università degli Studi di Milano = University of Milan (UNIMI), Instituto de Parasitología y Biomedicina 'López-Neyra' (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Granada = University of Granada (UGR), and Michel, Geneviève

Subjects
MESH: Databases, Protein, MESH: Inflammation, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Flow Cytometry, MESH: Cross-Sectional Studies, MESH: DNA Methylation, MESH: Computer Simulation, cell cycle, chronic lymphocytic leukemia, liquid chromatography-tandem mass spectrometry, splicing, MESH: Autoantibodies, MESH: Interferons, MESH: RNA-Seq, MESH: Cohort Studies, MESH: Databases, Genetic, MESH: Cytokines, MESH: Humans, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: Transcriptome, MESH: Adult, MESH: Chemokines, MESH: Male, MESH: Proteome, MESH: Sjogren's Syndrome, MESH: Genome-Wide Association Study, MESH: Biomarkers, MESH: Multigene Family, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Female, MESH: Computational Biology
Abstract

International audience; Abstract There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren’s syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials.

Published
2021
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32. Contributors

Author

Abdurakhmanov, Alexander, primary, Abu-Shakra, Mahmoud, additional, Afanasyeva, Marina, additional, Agmon-Levin, Nancy, additional, Albert, Paul J., additional, Almeida, Isabel, additional, Alves, Rute, additional, Amital, Howard, additional, Andrade, Paulo, additional, Antonelli, Alessandro, additional, Puccetti, Antonio, additional, Arango, María-Teresa, additional, Atzeni, Fabiola, additional, Baird, Alison E., additional, Balbir-Gurman, Alexandra, additional, Bashi, Tomer, additional, Batticciotto, Alberto, additional, Benucci, Maurizio, additional, Blank, Miri, additional, Bogdanos, Dimitrios P., additional, Bombardieri, S., additional, Borella, E., additional, Bosis, Samantha, additional, Bournia, Vasiliki Kalliopi, additional, Brandão, Mariana, additional, Braun-Moscovici, Yolanda, additional, Brender-Gotlieb, Neta, additional, Cainelli, Francesca, additional, Caldas, Cezar Augusto Muniz, additional, Campar, A., additional, Carvalheiras, Graziela, additional, Cervera, R., additional, Chapman, Joab, additional, Chastain, Emily M.L., additional, Claudio, Lunardi, additional, Cohen, Eytan, additional, Conti, Fabrizio, additional, Correia, J., additional, Carvalho, Jozélio Freire de, additional, Rossa, A. Della, additional, Detrick, Barbara, additional, Deutsch, Melanie, additional, Di Domenicantonio, Andrea, additional, Domeneghetti, M., additional, Domingues, Vital, additional, Doria, A., additional, Dow, Coad Thomas, additional, Dreyfus, David H., additional, Drouin, Elise E., additional, Dubaniewicz, Anna, additional, Durai, Malarvizhi, additional, Ebringer, Alan, additional, Ehrenfeld, Michael, additional, Elisa, Tinazzi, additional, Esposito, Susanna, additional, Fallahi, Poupak, additional, Faria, Raquel, additional, Farinha, Fátima, additional, Ferrannini, Ele, additional, Ferrari, Silvia Martina, additional, Ferreira, Alvaro, additional, Ferrão, C., additional, Garg, Ravindra Kumar, additional, Gatto, M., additional, Ghirardello, A., additional, Giovanna, Zanoni, additional, Giuseppe, Patuzzo, additional, Givaty, Gili, additional, Guilherme, Luiza, additional, Hammerstad, Sara Salehi, additional, Hodak, Emillia, additional, Hooks, John J., additional, Iaccarino, L., additional, Invernizzi, Pietro, additional, Israeli, Eitan, additional, Jamin, Christophe, additional, Janket, Sok-Ja, additional, Jarčuška, Peter, additional, Jones, Rodney P., additional, Kalil, Jorge, additional, Kanasi, Eleni, additional, Kivity, Shaye, additional, Konikoff, Tom, additional, Kozáková, D., additional, Krause, Ilan, additional, Lerner, Aaron, additional, Lidar, Merav, additional, Ling, Eduard, additional, Mahajna, Hussein, additional, Mahroum, Naim, additional, Maoz-Segal, Ramit, additional, Marinho, António, additional, Marshall, Trevor G., additional, Martinelli, Maria, additional, Marzia, Dolcino, additional, Mavragani, Clio P., additional, Mendonça, Teresa, additional, Miller, Stephen D., additional, Mimouni, Daniel, additional, Monteiro, Marta, additional, Moudgil, Kamal D., additional, Moulton, Vaishali R., additional, Moutsopoulos, Haralampos M., additional, Nagpal, Kamalpreet, additional, Neves, Esmeralda, additional, Nussenblatt, Robert, additional, Ollech, Ayelet, additional, Palma, L., additional, Pasoto, Sandra Gofinet, additional, Pella, Daniel, additional, Pereira, Cláudia, additional, Perricone, Carlo, additional, Petríková, Jana, additional, Proal, Amy D., additional, Rashid, Taha, additional, Reif, Shimon, additional, Renaudineau, Yves, additional, Ribeiro, Francinne Machado, additional, Rigante, Donato, additional, Rigopoulou, Eirini I., additional, Rose, Noel R., additional, Rosário, Cristina, additional, Rovenský, J., additional, Sakkas, Lazaros I., additional, Sarzi-Puttini, Piercarlo, additional, Seguro, Luciana Parente Costa, additional, Semino, Margherita, additional, Shoenfeld, Yehuda, additional, Silva, S., additional, Simonin, Laurent, additional, Smyk, Daniel S., additional, Sousa, Rita Catarina Medeiros, additional, Stagnaro, C., additional, Steere, Allen C., additional, Strle, Klemen, additional, Tektonidou, Maria G., additional, Tishler, Moshe, additional, Tomer, Yaron, additional, Toubi, Elias, additional, Tsokos, George C., additional, Vadasz, Zahava, additional, Valesini, Guido, additional, Vasconcelos, Carlos, additional, Vasconcelos, Júlia, additional, Vassilopoulos, Dimitrios, additional, Venkatesha, Shivaprasad H., additional, Vento, Sandro, additional, Viale, Christophe, additional, Villanueva, Ronald, additional, Vita, Pedro, additional, Wilson, Clyde, additional, Youinou, Pierre, additional, Záňová, E., additional, Zandman-Goddard, Gisele, additional, and Zen, M., additional

Published
2015
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36. Espectro Clínico dos Autoanticorpos TH/TO e NOR90 na Esclerose Sistémica

Author

Cravo, Márcia, Mendonça, Teresa, and Farinha, Fátima

Abstract

Introdução: A esclerose sistémica é uma doença autoimune com amplo espectro clínico. Os autoanticorpos podem indiciar sintomas, diagnósticos e orientar para o tratamento mais adequado. A relevância da pesquisa do anti-Th/To e anti-NOR 90 é menos conhecida. O objetivo foi avaliar as principais manifestações clínicas e diagnósticos etiológicos associados aos anticorpos Th/To e NOR 90. Material e Métodos: Estudo observacional retrospetivo, envolvendo 61 doentes em seguimento na consulta externa de doenças autoimunes com os anticorpos Th/To ou NOR90 positivos em centro único, entre 2018 e 2020. Foram excluídos os doentes sem informação disponível. Os dados demográficos, manifestações clínicas e diagnósticos foram analisados com recurso a informação dos processos informáticos. Resultados: Na amostra o género feminino foi o mais prevalente. Verificou-se envolvimento cutâneo, articular, cardiopulmonar e gastrointestinal, sem atingimento renal associado a nenhum dos autoanticorpos. Em ambos os grupos foi estabelecido diagnóstico de esclerose sistémica em 40% dos casos. Não se identificaram outros autoanticorpos concomitantes em 53% e 50% dos doentes com Th/To e NOR90, respetivamente. Discussão e Conclusão: Este estudo demonstrou envolvimento similar em ambos os autoanticorpos com atingimento cutâneo e articular frequentes, maior envolvimento cardiopulmonar nos doentes com anti-Th/To e gastrointestinal no grupo com anti-NOR90. Apesar de ambos se terem associado à esclerose sistémica numa percentagem não desprezível de doentes, em aproximadamente metade dos casos encontravam-se isolados, sem concomitância com outros autoanticorpos relacionados com esta doença, indiciando a relevância da sua pesquisa ativa aquando a suspeita clínica de esclerose sistémica com intuito diagnóstico., Medicina Interna, Vol. 28 N.º 2 (2021): Abril / Junho

Published
2021
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37. Clinical Spectrum of TH/TO and NOR90 Autoantibodies in Systemic Sclerosis

Author

Cravo, Márcia, Mendonça, Teresa, and Farinha, Fátima

Subjects
Sinais e Sintomas, Signs and Symptoms, Scleroderma, Systemic, Autoanticorpos, Esclerose Sistémica, Antibodies
Abstract

Introduction: Systemic sclerosis is an autoimmune disease with a large spectrum of clinical manifestations. Autoantibodies could indicate symptoms, diagnostics and establish a more appropriate treatment. The relevance of searching Th/To and NOR90 is still unknown. We aim to evaluate major manifestations and disease associations of Th/To and NOR90 autoantibodies. Material and Methods: Observational retrospective single-centre study, including all patients with Th/To or NOR90 autoantibodies followed in autoimmune consultation from 2018 to 2020. Absence of specific clinical information excluded patients. Demographic, clinical and diagnostical data were analysed. Results: In this study, female gender was the most prevalent. Cutaneous, articular, cardiopulmonary and gastrointestinal involvements were present in both autoantibodies’ groups, with no renal manifestations. In 40% of both groups, systemic sclerosis diagnosis was established. No other concomitant autoantibodies were documented in 53% and 50% of anti-Th/To and anti-NOR90, respectively. Discussion and Conclusion: This study verified similar involvement in both groups with frequent skin and articular symptoms, more cardiopulmonary involvement in anti-Th/To group and more gastrointestinal association in anti-NOR90. Although, in this study, these autoantibodies were commonly related to systemic sclerosis, in approximately half of cases they were isolated with no other concomitant systemic sclerosis’ autoantibodies, enhancing the importance of their active research when this disease is suspected.

Published
2021

38. ECOPOOL+++: DEVELOPING A SUSTAINABLE OUTDOOR HEATED SWIMMING POOL.

Author

José Oliveira, Miguel, Inverno, Armando, Farinha, Fátima, Monteiro, Jânio, Cabrita, Cristiano, Segura, Maria, do Carmo, Francisco, Venturinha, Adelino, and Matias, Gina

Subjects
SWIMMING pools, SUSTAINABLE development, CLIMATE change, CONSTRUCTION industry, CONSTRUCTION materials
Abstract

The University of Algarve, in consortium with "Cristal Construções - Materiais e Obras de Construção Civil", "Itelmatis Control Systems" and "Itecons - Instituto de Investigação e Desenvolvimento Tecnológico para a Construção, Energia, Ambiente e Sustentabilidade", is developing a new concept of outdoor heated sustainable swimming pool, having a higher energy efficiency and lower environmental footprint. The main objective is to minimise energy and water consumptions, while assuring a comfortable temperature for the user, extending the utilization of the pool in the Algarve region, from the summer months, to at least 8 months of the year. In order to do it, different systems will be tested, including solar thermal and photovoltaic panels, inverted underfloor heating, heat accumulator exchanger with phase change materials and energy dissipating pipes. An innovative thermal insulation system will be included in the interior of the pool tank, together with a new system for the covering of the water plane. All these systems will be monitored and controlled by an industrial automation system that will communicate, via a programmable logic controller, using industry standard communication protocols, with a SMART platform, that will be in charge of the global operation's optimisation. This platform will support an intelligent and predictive control and monitoring module, that controls the automation system to maximize the energy usage of the renewable sources, while assuring the user preferences. One of the main outputs of this project is the construction of a smaller scale prototype of a swimming pool, with the characteristics mentioned above, in order to test and validate the proposed developments. [ABSTRACT FROM AUTHOR]

Published
2022
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40. Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Author

Teruel, María, Barturen, Guillermo, Martínez Bueno, Manuel, Castellini Pérez, Olivia, Barroso Gil, Miguel, Povedano, Elena, Kerick, Martin, Català Moll, Francesc, Makowska, Zuzanna, Buttgereit, Anne, Beretta, Lorenzo, Chizzolini, Carlo, Zuber, Aleksandra, Wynar, Donatienne, Kovács, Laszló, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Rodriguez Maresca, Manuel, López Berrio, Antonio, Aguilar Quesada, Rocío, Navarro Linares, Héctor, Alvarez, Montserrat, Álvarez Errico, Damiana, Azevedo, Nancy, Barbarroja, Nuria, Cheng, Qingyu, Cremer, Jonathan, Groof, Aurélie de, Langhe, Ellen de, Ducreux, Julie, Dufour, Aleksandra, Hernández Fuentes, María, Khodadadi, Laleh, Kniesch, Katja, Li, Tianlu, López Pedrera, Chary, Marañón, Concepción, Muchmore, Brian, Neves, Esmeralda, Rouvière, Bénédicte, Simon, Quentin, Trombetta, Elena, Varela, Nieves, Witte, Torsten, Pers, Jacques-olivier, Ballestar, Esteban, Martin, Javier, Carnero Montoro, Elena, Alarcón Riquelme, Marta, Precisesads Clinical Consortium, Precisesads Flow Cytometry Study Group, Vigone, Barbara, Pers, Jacques Olivier, Saraux, Alain, Devauchelle-Pensec, Valérie, Cornec, Divi, Jousse-Joulin, Sandrine, Lauwerys, Bernard, Maudoux, Anne-lise, Vasconcelos, Carlos, Tavares, Ana, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Ángel, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Cervera, Ricard, Rodríguez Pintó, Ignasi, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega Castro, Rafaela, Aguirre Zamorano, Mª Angeles, Escudero Contreras, Alejandro, Castro Villegas, Mª Carmen, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Jiménez Moleón, Inmaculada, Ramon, Enrique de, Díaz Quintero, Isabel, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, PRECISESADS Clinical Consortium, PRECISESADS Flow Cytometry Study Group, [Teruel,M, Barturen,G, Martínez-Bueno,M, Castellini-Pérez,O, Barroso-Gil,M, Povedano,E, Marañón,C, Carnero-Montoro,E, Alarcón-Riquelme,ME] GENYO, Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain. [Kerick,M, Martin,J] IPBLN-CSIC, Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científcas, Granada, Spain. [Català-Moll,F, Ballestar,E] Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), Badalona, Barcelona, Spain. [Català-Moll,F, Ballestar,E] IDIBELL, Bellvitge Biomedical Research Institute L’Hospitalet de Llobregat, Barcelona, Spain. [Makowska,Z, Buttgereit,A] Pharmaceuticals Division, Bayer Pharma Aktiengesellschaft, Berlin, Germany. [Pers,JO] Université de Brest, INSERM, Labex IGO, CHU de Brest, Brest, France.[Alarcón-Riquelme,ME] Institute for Environmental Medicine, Karolinska Institutet, Solna, Sweden., and Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement nº 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies’ in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucía (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuró for design support.

Subjects
Epigenomics, Male, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation [Medical Subject Headings], Autoimmune diseases, Gene Expression, Quantitative trait, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Interferons [Medical Subject Headings], 0302 clinical medicine, Rheumatic diseases, HLA Antigens, Genetics, Regulation of gene expression, 0303 health sciences, education.field_of_study, Multidisciplinary, Malalties autoimmunitàries, Molecular medicine, Epigenetic, Autoanticuerpos, Genomics, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Epigenomics [Medical Subject Headings], 3. Good health, Sjogren's Syndrome, DNA methylation, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::DNA Methylation [Medical Subject Headings], Medicine, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens [Medical Subject Headings], Epigenetics, Female, Phenomena and Processes::Genetic Phenomena::Genetic Variation [Medical Subject Headings], Extracellular matrix organization, Science, Population, Check Tags::Male [Medical Subject Headings], Human leukocyte antigen, Biology, Variación genética, Article, 03 medical and health sciences, Rheumatology, Enfermedades autoinmunes, Diseases::Immune System Diseases::Autoimmune Diseases [Medical Subject Headings], Immunogenetics, Diseases::Immune System Diseases::Autoimmune Diseases::Arthritis, Rheumatoid::Sjogren's Syndrome [Medical Subject Headings], Humans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies [Medical Subject Headings], education, Gene, 030304 developmental biology, Autoantibodies, 030203 arthritis & rheumatology, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Genetic Variation, DNA Methylation, Epigenètica, Check Tags::Female [Medical Subject Headings], Gene Expression Regulation, Epigenómica, Síndrome de Sjögren, Interferons, Expresión génica
Abstract

Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies' in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucia (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuro for design support., Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population., Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Program (FP7/2007-2013) 115,565, EFPIA companies, Junta de Andalucia PI/0017/2016, Innovative Medicines Initiative 2 Joint Undertaking 806975 European Union's Horizon 2020 research and innovation programme, EFPIA, Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness FJCI_2014_20652

Published
2021

41. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases.

Author

UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alarcón-Riquelme, Marta E, Benschop, Robert J, Balog, Attila, Bocskai, Márta, Deák, Magdolna, Dulic, Sonja, Kádár, Gabriella, Kovács, László, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Chamberlain, Chris, Dufour, Aleksandra, Dow, Ernst R, Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegård, Johan, Martín, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Wynar, Donatienne, Barturen, Guillermo, Babaei, Sepideh, Català-Moll, Francesc, Martínez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugán, Jordi, Carmona-Sáez, Pedro, Toro-Domínguez, Daniel, Carnero-Montoro, Elena, Teruel, María, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodríguez-Ubreva, Javier, García-Gómez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Marañón, Concepción, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocío, Garrancho, Francisco Javier, López-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Héctor, Almeida, Isabel, Azevedo, Nancy, Brandão, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fátima, Marinho, António, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Genre, Fernanda, López Mejías, Raquel, Gonzalez-Gay, Miguel A, Remuzgo, Sara, Ubilla Garcia, Begoña, Cervera, Ricard, Espinosa, Gerard, Rodríguez-Pintó, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Díaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernández Roldán, María Concepción, Jiménez Gómez, Yolanda, Jiménez Moleón, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurélie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valérie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouvière, Bénédicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alarcón-Riquelme, Marta E, Benschop, Robert J, Balog, Attila, Bocskai, Márta, Deák, Magdolna, Dulic, Sonja, Kádár, Gabriella, Kovács, László, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Chamberlain, Chris, Dufour, Aleksandra, Dow, Ernst R, Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegård, Johan, Martín, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Wynar, Donatienne, Barturen, Guillermo, Babaei, Sepideh, Català-Moll, Francesc, Martínez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugán, Jordi, Carmona-Sáez, Pedro, Toro-Domínguez, Daniel, Carnero-Montoro, Elena, Teruel, María, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodríguez-Ubreva, Javier, García-Gómez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Marañón, Concepción, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocío, Garrancho, Francisco Javier, López-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Héctor, Almeida, Isabel, Azevedo, Nancy, Brandão, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fátima, Marinho, António, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Genre, Fernanda, López Mejías, Raquel, Gonzalez-Gay, Miguel A, Remuzgo, Sara, Ubilla Garcia, Begoña, Cervera, Ricard, Espinosa, Gerard, Rodríguez-Pintó, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Díaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernández Roldán, María Concepción, Jiménez Gómez, Yolanda, Jiménez Moleón, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurélie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valérie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouvière, Bénédicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, and Chizzolini, Carlo

Abstract

OBJECTIVE: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. METHODS: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. RESULTS: Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. CONCLUSION: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.

Published
2021

45. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author

Barturen, Guillermo, primary, Babaei, Sepideh, additional, Català‐Moll, Francesc, additional, Martínez‐Bueno, Manuel, additional, Makowska, Zuzanna, additional, Martorell‐Marugán, Jordi, additional, Carmona‐Sáez, Pedro, additional, Toro‐Domínguez, Daniel, additional, Carnero‐Montoro, Elena, additional, Teruel, María, additional, Kerick, Martin, additional, Acosta‐Herrera, Marialbert, additional, Le Lann, Lucas, additional, Jamin, Christophe, additional, Rodríguez‐Ubreva, Javier, additional, García‐Gómez, Antonio, additional, Kageyama, Jorge, additional, Buttgereit, Anne, additional, Hayat, Sikander, additional, Mueller, Joerg, additional, Lesche, Ralf, additional, Hernandez‐Fuentes, Maria, additional, Juarez, Maria, additional, Rowley, Tania, additional, White, Ian, additional, Marañón, Concepción, additional, Gomes Anjos, Tania, additional, Varela, Nieves, additional, Aguilar‐Quesada, Rocío, additional, Garrancho, Francisco Javier, additional, López‐Berrio, Antonio, additional, Rodriguez Maresca, Manuel, additional, Navarro‐Linares, Héctor, additional, Almeida, Isabel, additional, Azevedo, Nancy, additional, Brandão, Mariana, additional, Campar, Ana, additional, Faria, Raquel, additional, Farinha, Fátima, additional, Marinho, António, additional, Neves, Esmeralda, additional, Tavares, Ana, additional, Vasconcelos, Carlos, additional, Trombetta, Elena, additional, Montanelli, Gaia, additional, Vigone, Barbara, additional, Alvarez‐Errico, Damiana, additional, Li, Tianlu, additional, Thiagaran, Divya, additional, Blanco Alonso, Ricardo, additional, Corrales Martínez, Alfonso, additional, Genre, Fernanda, additional, López Mejías, Raquel, additional, Gonzalez‐Gay, Miguel A., additional, Remuzgo, Sara, additional, Ubilla Garcia, Begoña, additional, Cervera, Ricard, additional, Espinosa, Gerard, additional, Rodríguez‐Pintó, Ignasi, additional, De Langhe, Ellen, additional, Cremer, Jonathan, additional, Lories, Rik, additional, Belz, Doreen, additional, Hunzelmann, Nicolas, additional, Baerlecken, Niklas, additional, Kniesch, Katja, additional, Witte, Torsten, additional, Lehner, Michaela, additional, Stummvoll, Georg, additional, Zauner, Michael, additional, Aguirre‐Zamorano, Maria Angeles, additional, Barbarroja, Nuria, additional, Castro‐Villegas, Maria Carmen, additional, Collantes‐Estevez, Eduardo, additional, Ramon, Enrique, additional, Díaz Quintero, Isabel, additional, Escudero‐Contreras, Alejandro, additional, Fernández Roldán, María Concepción, additional, Jiménez Gómez, Yolanda, additional, Jiménez Moleón, Inmaculada, additional, Lopez‐Pedrera, Rosario, additional, Ortega‐Castro, Rafaela, additional, Ortego, Norberto, additional, Raya, Enrique, additional, Artusi, Carolina, additional, Gerosa, Maria, additional, Meroni, Pier Luigi, additional, Schioppo, Tommaso, additional, De Groof, Aurélie, additional, Ducreux, Julie, additional, Lauwerys, Bernard, additional, Maudoux, Anne‐Lise, additional, Cornec, Divi, additional, Devauchelle‐Pensec, Valérie, additional, Jousse‐Joulin, Sandrine, additional, Jouve, Pierre‐Emmanuel, additional, Rouvière, Bénédicte, additional, Saraux, Alain, additional, Simon, Quentin, additional, Alvarez, Montserrat, additional, Chizzolini, Carlo, additional, Dufour, Aleksandra, additional, Wynar, Donatienne, additional, Balog, Attila, additional, Bocskai, Márta, additional, Deák, Magdolna, additional, Dulic, Sonja, additional, Kádár, Gabriella, additional, Kovács, László, additional, Cheng, Qingyu, additional, Gerl, Velia, additional, Hiepe, Falk, additional, Khodadadi, Laleh, additional, Thiel, Silvia, additional, Rinaldis, Emanuele, additional, Rao, Sambasiva, additional, Benschop, Robert J., additional, Chamberlain, Chris, additional, Dow, Ernst R., additional, Ioannou, Yiannis, additional, Laigle, Laurence, additional, Marovac, Jacqueline, additional, Wojcik, Jerome, additional, Renaudineau, Yves, additional, Borghi, Maria Orietta, additional, Frostegård, Johan, additional, Martín, Javier, additional, Beretta, Lorenzo, additional, Ballestar, Esteban, additional, McDonald, Fiona, additional, Pers, Jacques‐Olivier, additional, and Alarcón‐Riquelme, Marta E., additional

Published
2021
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46. Evaluating the potential of adaptive comfort approach using historic data to reduce energy consumption in buildings in southern Spain

Author

Universidad de Sevilla. Departamento de Construcciones Arquitectónicas II (ETSIE), Universidad de Sevilla. RNM162: Composición, Arquitectura y Medio Ambiente, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Junta de Andalucía, Bienvenido Huertas, José David, Rubio Bellido, Carlos, Farinha, Fátima, Oliveira, Miguel José, Pérez Ordóñez, Juan Luis, Universidad de Sevilla. Departamento de Construcciones Arquitectónicas II (ETSIE), Universidad de Sevilla. RNM162: Composición, Arquitectura y Medio Ambiente, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Junta de Andalucía, Bienvenido Huertas, José David, Rubio Bellido, Carlos, Farinha, Fátima, Oliveira, Miguel José, and Pérez Ordóñez, Juan Luis

Abstract

The application of adaptive comfort models is among the determinant factors to reduce greenhouse gas emissions in the building sector. This research studies the region of Andalusia (south of Spain). A cluster analysis is applied to 786 Andalusian municipalities, and 4 groups are established according to the potential of adaptive strategies. A town is chosen from each group, and an hourly specific study is conducted for the last 20 years, as well as a daily study of the old time series by using an artificial neural network based on the existing climate data. The possibility of application of the EN 16798–1:2019 standard during the days of the year is analysed, as well as the possibilities of using natural ventilation and the possibility of using adaptive setpoint temperatures in comparison with both 3 fixed heating temperatures and 3 fixed cooling temperatures by considering the energy saving. The results to apply the standard ranged 69.0 and 100% of the days of each year. The possibilities of natural ventilation considered were greater than 10% of the hours of the year in all the assumptions. The energy saving of cooling degrees reveals a greater potential in the area studied than that of heating degrees; this tendency is supported by the study of old temporary series which are part of the climate variation predicted throughout the 21st century.

Published
2020

50. O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

Author

Barturen, Guillermo, primary, Babaei, Sepideh, additional, Català-Moll, Francesc, additional, Martínez-Bueno, Manuel, additional, Makowska, Zuzanna, additional, Martorell-Marugán, Jordi, additional, Carmona-Sáez, Pedro, additional, Toro-Domínguez, Daniel, additional, Carnero-Montoro, Elena, additional, Kerick, Martin, additional, Acosta-Herrera, Marialbert, additional, Lann, Lucas Le, additional, Jamin, Christophe, additional, Rodríguez-Ubreva, Javier, additional, García-Gómez, Antonio, additional, Kageyama, Jorge, additional, Buttgereit, Anne, additional, Hayat, Sikander, additional, Mueller, Joerg, additional, Lesche, Ralf, additional, Hernandez-Fuentes, Maria, additional, Juarez, Maria, additional, Rowley, Tania, additional, White, Ian, additional, Marañón, Concepción, additional, Anjos, Tania Gomes, additional, Varela, Nieves, additional, Aguilar-Quesada, Rocío, additional, Garrancho, Francisco Javier, additional, López-Berrio, Antonio, additional, Maresca, Manuel Rodriguez, additional, Navarro-Linares, Héctor, additional, Almeida, Isabel, additional, Azevedo, Nancy, additional, Brandão, Mariana, additional, Campar, Ana, additional, Faria, Raquel, additional, Farinha, Fátima, additional, Marinho, António, additional, Neves, Esmeralda, additional, Tavares, Ana, additional, Vasconcelos, Carlos, additional, Trombetta, Elena, additional, Montanelli, Gaia, additional, Vigone, Barbara, additional, Alvarez-Errico, Damiana, additional, Li, Tianlu, additional, Alonso, Ricardo Blanco, additional, Martínez, Alfonso Corrales, additional, Genre, Fernanda, additional, Mejías, Raquel López, additional, Gonzalez-Gay, Miguel A, additional, Remuzgo, Sara, additional, Garcia, Begoña Ubilla, additional, Cervera, Ricard, additional, Espinosa, Gerard, additional, Rodríguez-Pintó, Ignasi, additional, Langhe, Ellen De, additional, Cremer, Jonathan, additional, Lories, Rik, additional, Belz, Doreen, additional, Hunzelmann, Nicolas, additional, Baerlecken, Niklas, additional, Kniesch, Katja, additional, Witte, Torsten, additional, Lehner, Michaela, additional, Stummvoll, Georg, additional, Zauner, Michael, additional, Aguirre-Zamorano, Maria Angeles, additional, Barbarroja, Nuria, additional, Castro-Villegas, Maria Carmen, additional, Collantes-Estevez, Eduardo, additional, Ramon, Enrique de, additional, Quintero, Isabel Díaz, additional, Escudero-Contreras, Alejandro, additional, Roldán, María Concepción Fernández, additional, Gómez, Yolanda Jiménez, additional, Moleón, Inmaculada Jiménez, additional, Lopez-Pedrera, Rosario, additional, Ortega-Castro, Rafaela, additional, Ortego, Norberto, additional, Raya, Enrique, additional, Artusi, Carolina, additional, Gerosa, Maria, additional, Meroni, Pier Luigi, additional, Schioppo, Tommaso, additional, Groof, Aurélie De, additional, Ducreux, Julie, additional, Lauwerys, Bernard, additional, Maudoux, Anne-Lise, additional, Cornec, Divi, additional, Devauchelle-Pensec, Valérie, additional, Jousse-Joulin, Sandrine, additional, Jouve, Pierre-Emmanuel, additional, Rouvière, Bénédicte, additional, Saraux, Alain, additional, Simon, Quentin, additional, Alvarez, Montserrat, additional, Chizzolini, Carlo, additional, Dufour, Aleksandra, additional, Wynar, Donatienne, additional, Balog, Attila, additional, Bocskai, Márta, additional, Deák, Magdolna, additional, Dulic, Sonja, additional, Kádár, Gabriella, additional, Kovács, László, additional, Cheng, Qingyu, additional, Gerl, Velia, additional, Hiepe, Falk, additional, Khodadadi, Laleh, additional, Thiel, Silvia, additional, Rinaldis, Emanuele de, additional, Rao, Sambasiva, additional, Benschop, Robert J, additional, Chamberlain, Chris, additional, Dow, Ernst R, additional, Ioannou, Yiannis, additional, Laigle, Laurence, additional, Marovac, Jacqueline, additional, Wojcik, Jerome, additional, Renaudineau, Yves, additional, Borghi, Maria Orietta, additional, Frostegård, Johan, additional, Martín, Javier, additional, Beretta, Lorenzo, additional, Ballestar, Esteban, additional, McDonald, Fiona, additional, Pers, Jacques-Olivier, additional, and Alarcón-Riquelme, Marta E, additional

Published
2020
Full Text
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