Prognostic and predictive markers of treatment response in autoimmune disease

Our group’s main goal is personalised medicine in the field of autoimmune/inflammatory rheumatic disorders (mainly arthritis, spondyloarthritis, systemic lupus erythematosus, giant cell arteritis and scleroderma). Our efforts focus on providing new knowledge about two unmet needs for rheumatologists: biomarkers of severity and predictors of response to biological therapies. In the last five years, to achieve these goals, we have consolidated our collaborations both locally within our Institute and nationally.

In 2013 we participated in the development of the BioIMID project, which was selected for funding by the PIE programme (Integrated Projects of Excellence for Health Research Institutes) at the (ISCIII). This project aims to deepen personalised medicine in the field of biological therapies for immune-mediated inflammatory diseases. Eight groups from our Institute participate in BioIMID, coordinated by Dr Mónica Marazuela, and the Biological Therapies Unit, directed by Dr Alvaro-Gracia, plays a key role in the project.

On the other hand, we maintain strong collaboration ties with groups from the Red de Inflamación y Enfermedades Reumáticas (RIER, Inflammation and Rheumatic Diseases Network), which is part of ISCIII’s RETICS programme. Our research is mainly focused on detecting prognostic factors and cardiovascular risk in rheumatoid arthritis, as well as studying safety aspects in biological therapies. Many other rheumatological diseases, such as scleroderma, systemic lupus erythematosus, systemic vasculitis and osteoporosis are also the object of the work carried out by our researchers.

As a result of the group’s intense activity, some of its members have been required to participate in preparing several documents to establish consensus guidelines for the rational use of biological therapies or imaging techniques in which an appropriate cost/benefit ratio is very important in the current economic situation. Group members have also developed two patents.

Over the next few years, our efforts will continue to focus on the discovery of new biomarkers that allow patients to be treated more efficiently. The main objective is the application of the discoveries protected by our patents and their transfer to industry. We may thus offer society some tools that can establish more efficient therapeutic programmes for the diseases in which we are interested.

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Team members
 

area3_dr-Isidoro_Gonzalez_alvaro

Group leader:

Isidoro González Álvaro

Hospital Universitario La Princesa

   Other team members. Hospital Universitario La Princesa:

  • José María Álvaro-Gracia Álvaro
  • Santos Castañeda Sanz
  • Rosario García de Vicuña Pinedo
  • Jesús Alberto García Vadillo
  • María de las Nieves Gómez León
  • Amalia Lamana Domínguez
  • Irene Llorente Cubas
  • Nuria Montes Casado
  • Ana María Ortiz García
  • Eva Gloria Tomero Muriel
  • Ana Triguero Martínez
  • Miren Uriarte Ecenarro
  • Esther Francisca Vicente Rabaneda

González Álvaro, Isidoro. Red de Inflamación y Enfermedades Reumáticas (RIER). RD16/0012/0011. ISCIII. 2017-2021.

This grant is funded by the 2013-2016 Spanish Science, Technology and Innovation Research Plan and the ISCIII – Subdirectorate General for Evaluation and Promotion of Research – and co-financed by the European Regional Development Fund, Operational Programme Smart Growth 2014-2020 according to Regulation (EU) no. 1303/2013.

González Álvaro, Isidoro. Immunoregulatory molecules as biomarkers predicting response to biological therapies and disease severity in immune-mediated inflammatory disorders. BIOMID PROJECT. PIE13/00041. Coordinated project. ISCIII. 2014-2016.

García Vadillo, Jesús Alberto. El TBS en mujeres postmenopáusicas con fractura de antebrazo por traumatismo de baja energía. SEIOMM. 2014-2015.

Castañeda Sanz, Santos. OBSERVAR: Observancia al tratamiento con FAMES en artritis reumatoide. Laboratorio ROCHE. 2014-2015.

Tomero Muriel, Eva Gloria. Relesser-pro. Registro prospectivo español de pacientes con lupus eritematoso sistémico. SER. 2014-2019.

González Álvaro, Isidoro. RIER: Red de investigación en inflamación y enfermedades reumáticas. RD12/0009/0017. ISCIII. 2013-2016.

Castañeda Sanz, Santos. Valor predictivo de la variación mineral ósea cortical en manos determinada mediante densitometría dual como marcador pronostico en pacientes con artritis de inicio. PI12/01578. ISCIII. 2013-2015.

González Álvaro, Isidoro. Desarrollo de un sistema de apoyo a las decisiones basado en técnicas de inteligencia artificial para el manejo rutinario de la artritis reumatoide. PI14/00442. ISCIII. 2015-2017.

Lamana Domínguez, Amalia. Estudio de la expresión génica y mecanismos de regulación de VIP y sus receptores en artritis de reciente comienzo. Validación como marcador pronóstico. PI14/01236. ISCIII. 2015-2017.

González Álvaro, Isidoro. Desarrollo y validación clínica de un sistema de análisis de biomarcadores genéticos y/o epigenéticos para personalizar el tratamiento en enfermedades inflamatorias y autoinmunes. RTC-2015-3562-1. MINECO. 2015-2018.

Castañeda Sanz, Santos. New approaches to rare respiratory orphan fibrotic diseases with locally administered targeted nanoparticles. AC17/00027. ISCIII. 2018-2020.

This grant is funded by the 2013-2016 Spanish Science, Technology and Innovation Research Plan and the ISCIII – Subdirectorate General for Evaluation and Promotion of Research – and co-financed by the European Regional Development Fund, Operational Programme Smart Growth 2014-2020 according to Regulation (EU) no. 1303/2013.

González Álvaro, Isidoro. Predicción en la evolución de la Artritis Reumatoide mediante técnicas de “machine learning”. PI18/00371. ISCIII. 2019-2021.

Aplicación de herramientas de “machine learning” para desarrollar modelos predictivos de la evolución de pacientes con artritis reumatoide.

This grant is funded by the 2017-2020 Spanish Science, Technology and Innovation Research Plan and the ISCIII – Subdirectorate General for Evaluation and Promotion of Research – and co-financed by the European Regional Development Fund, Operational Programme Smart Growth 2014-2020 according to Regulation (EU) no. 1303/2013.

González-Álvaro I, Martínez-Fernández C, Dorantes-Calderón B, García-Vicuña R, Hernández-Cruz B, Herrero-Ambrosio A, Ibarra-Barrueta O, Martín-Mola E, Monte-Boquet E, Morell-Baladrón A, Sanmartí R, Sanz-Sanz J, de Toro-Santos FJ, Vela P, Román Ivorra JA, Poveda-Andrés JL, Muñoz-Fernández S. Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations for biologics optimization in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Rheumatology (Oxford) 2015. 54: 1200-1209. FI: 4.475(Q1). PMID: 25526976. DOI: 10.1093/rheumatology/keu461.

Martínez C, Ortiz AM, Juarranz Y, Lamana A, Seoane IV, Leceta J, García-Vicuña R, Gomariz RP, González-Álvaro I. Serum Levels of Vasoactive Intestinal Peptide as a Prognostic Marker in Early Arthritis. PLoS One 2014. FI: 3.234(Q1). PMID: 24409325. DOI: 10.1371/journal.pone.0085248.

Bossini-Castillo L, de Kovel C, Kallberg H, van ‘t Slot R, Italiaander A, Coenen M, Tak PP, Posthumus MD, Wijmenga C, Huizinga T, van der Helm-van Mil AH, Stoeken-Rijsbergen G, Rodriguez-Rodriguez L, Balsa A, González-Álvaro I, González-Gay MÁ, Gómez-Vaquero C, Franke B, LifeLines Cohort Study, Vermeulen S, van der Horst-Bruinsma Ie, Dijkmans BA, Wolbink GJ, Ophoff RA, Maehlen MT, van Riel P, Merriman M, Klareskog L, Lie BA, Merriman T, Crusius JB, Brouwer E, Martin J, de Vries N, Toes R, Padyukov L, Koeleman BP. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides.. Ann Rheum Dis 2015. . FI: 10.377(Q1). PMID: 24532677. DOI: 10.1136/annrheumdis-2013-204591.

Castrejón I, Carmona L, Ortiz AM, Belmonte MA, Martínez-López JA, González-Álvaro I. Development and Validation of a New Disease Activity Index as a Numerical Sum of Four Variables in Patients With Early Arthritis. Arthritis Care Res. 2013. 65: 518-525. FI: 4.039(Q2). PMID: 23002022. DOI: 10.1002/acr.21854.

Ibañez M, Ortiz AM, Castrejón I, García-Vadillo JA, Carvajal I, Castañeda S, González-Alvaro I. A rational use of glucocorticoids in patients with early arthritis has a minimal impact on bone mass. Arthritis Res Ther 2010. FI: 4.357(Q2). PMID: 20331862. DOI: 10.1186/ar2961.