Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling
IntroductionRA patients are at higher risk of cardiovascular disease, influenced by therapies. Studying their cardiovascular and cardiometabolic proteome can unveil biomarkers and insights into related biological pathways.MethodsThis study included two cohorts of RA patients: newly diagnosed individ...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1333995/full |
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| author | Laura Cuesta-López Alejandro Escudero-Contreras Yas Hanaee Yas Hanaee Carlos Pérez-Sánchez Carlos Pérez-Sánchez Carlos Pérez-Sánchez Miriam Ruiz-Ponce Julio Manuel Martínez-Moreno Eva Pérez-Pampin Antonio González Chamaida Plasencia-Rodriguez Ana Martínez-Feito Alejandro Balsa Clementina López-Medina Lourdes Ladehesa-Pineda Marta Rojas-Giménez Rafaela Ortega-Castro Jerusalem Calvo-Gutiérrez Chary López-Pedrera Eduardo Collantes-Estévez Iván Arias-de la Rosa Nuria Barbarroja Nuria Barbarroja |
| author_facet | Laura Cuesta-López Alejandro Escudero-Contreras Yas Hanaee Yas Hanaee Carlos Pérez-Sánchez Carlos Pérez-Sánchez Carlos Pérez-Sánchez Miriam Ruiz-Ponce Julio Manuel Martínez-Moreno Eva Pérez-Pampin Antonio González Chamaida Plasencia-Rodriguez Ana Martínez-Feito Alejandro Balsa Clementina López-Medina Lourdes Ladehesa-Pineda Marta Rojas-Giménez Rafaela Ortega-Castro Jerusalem Calvo-Gutiérrez Chary López-Pedrera Eduardo Collantes-Estévez Iván Arias-de la Rosa Nuria Barbarroja Nuria Barbarroja |
| author_sort | Laura Cuesta-López |
| collection | DOAJ |
| description | IntroductionRA patients are at higher risk of cardiovascular disease, influenced by therapies. Studying their cardiovascular and cardiometabolic proteome can unveil biomarkers and insights into related biological pathways.MethodsThis study included two cohorts of RA patients: newly diagnosed individuals (n=25) and those with established RA (disease duration >25 years, n=25). Both cohorts were age and sex-matched with a control group (n=25). Additionally, a longitudinal investigation was conducted on a cohort of 25 RA patients treated with methotrexate and another cohort of 25 RA patients treated with tofacitinib for 6 months. Clinical and analytical variables were recorded, and serum profiling of 184 proteins was performed using the Olink technology platform. ResultsRA patients exhibited elevated levels of 75 proteins that might be associated with cardiovascular disease. In addition, 24 proteins were increased in RA patients with established disease. Twenty proteins were commonly altered in both cohorts of RA patients. Among these, elevated levels of CTSL1, SORT1, SAA4, TNFRSF10A, ST6GAL1 and CCL18 discriminated RA patients and HDs with high specificity and sensitivity. Methotrexate treatment significantly reduced the levels of 13 proteins, while tofacitinib therapy modulated the expression of 10 proteins. These reductions were associated with a decrease in DAS28. Baseline levels of SAA4 and high levels of BNP were associated to the non-response to methotrexate. Changes in IL6 levels were specifically linked to the response to methotrexate. Regarding tofacitinib, differences in baseline levels of LOX1 and CNDP1 were noted between non-responder and responder RA patients. In addition, response to tofacitinib correlated with changes in SAA4 and TIMD4 levels. ConclusionIn summary, this study pinpoints molecular changes linked to cardiovascular disease in RA and proposes candidate protein biomarkers for distinguishing RA patients from healthy individuals. It also highlights how methotrexate and tofacitinib impact these proteins, with distinct alterations corresponding to each drug’s response, identifying potential candidates, as SAA4, for the response to these therapies. |
| first_indexed | 2024-03-08T01:49:09Z |
| format | Article |
| id | doaj.art-9316ccf43261484ca067d2fe59890167 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T01:49:09Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9316ccf43261484ca067d2fe598901672024-02-14T11:44:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13339951333995Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profilingLaura Cuesta-López0Alejandro Escudero-Contreras1Yas Hanaee2Yas Hanaee3Carlos Pérez-Sánchez4Carlos Pérez-Sánchez5Carlos Pérez-Sánchez6Miriam Ruiz-Ponce7Julio Manuel Martínez-Moreno8Eva Pérez-Pampin9Antonio González10Chamaida Plasencia-Rodriguez11Ana Martínez-Feito12Alejandro Balsa13Clementina López-Medina14Lourdes Ladehesa-Pineda15Marta Rojas-Giménez16Rafaela Ortega-Castro17Jerusalem Calvo-Gutiérrez18Chary López-Pedrera19Eduardo Collantes-Estévez20Iván Arias-de la Rosa21Nuria Barbarroja22Nuria Barbarroja23Rheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainScientific department, Cobiomic Bioscience S.L, Cordoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainScientific department, Cobiomic Bioscience S.L, Cordoba, SpainDepartment of Cell Biology, Immunology and Physiology, Agrifood Campus of International Excellence, University of Córdoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainScientific department, Cobiomic Bioscience S.L, Cordoba, SpainExperimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigación Sanitaria - Hospital Clínico Universitario de Santiago (IDIS), Santiago de Compostela, Galicia, SpainExperimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigación Sanitaria - Hospital Clínico Universitario de Santiago (IDIS), Santiago de Compostela, Galicia, SpainRheumatology Department, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ) Institute for Health Research, La Paz University Hospital, Madrid, SpainRheumatology Department, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ) Institute for Health Research, La Paz University Hospital, Madrid, SpainRheumatology Department, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ) Institute for Health Research, La Paz University Hospital, Madrid, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainRheumatology Service, Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, SpainScientific department, Cobiomic Bioscience S.L, Cordoba, SpainIntroductionRA patients are at higher risk of cardiovascular disease, influenced by therapies. Studying their cardiovascular and cardiometabolic proteome can unveil biomarkers and insights into related biological pathways.MethodsThis study included two cohorts of RA patients: newly diagnosed individuals (n=25) and those with established RA (disease duration >25 years, n=25). Both cohorts were age and sex-matched with a control group (n=25). Additionally, a longitudinal investigation was conducted on a cohort of 25 RA patients treated with methotrexate and another cohort of 25 RA patients treated with tofacitinib for 6 months. Clinical and analytical variables were recorded, and serum profiling of 184 proteins was performed using the Olink technology platform. ResultsRA patients exhibited elevated levels of 75 proteins that might be associated with cardiovascular disease. In addition, 24 proteins were increased in RA patients with established disease. Twenty proteins were commonly altered in both cohorts of RA patients. Among these, elevated levels of CTSL1, SORT1, SAA4, TNFRSF10A, ST6GAL1 and CCL18 discriminated RA patients and HDs with high specificity and sensitivity. Methotrexate treatment significantly reduced the levels of 13 proteins, while tofacitinib therapy modulated the expression of 10 proteins. These reductions were associated with a decrease in DAS28. Baseline levels of SAA4 and high levels of BNP were associated to the non-response to methotrexate. Changes in IL6 levels were specifically linked to the response to methotrexate. Regarding tofacitinib, differences in baseline levels of LOX1 and CNDP1 were noted between non-responder and responder RA patients. In addition, response to tofacitinib correlated with changes in SAA4 and TIMD4 levels. ConclusionIn summary, this study pinpoints molecular changes linked to cardiovascular disease in RA and proposes candidate protein biomarkers for distinguishing RA patients from healthy individuals. It also highlights how methotrexate and tofacitinib impact these proteins, with distinct alterations corresponding to each drug’s response, identifying potential candidates, as SAA4, for the response to these therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1333995/fullrheumatoid arthritismethotrexatetofacitinibbiomarkersproximity extension assay (PEA)Olink |
| spellingShingle | Laura Cuesta-López Alejandro Escudero-Contreras Yas Hanaee Yas Hanaee Carlos Pérez-Sánchez Carlos Pérez-Sánchez Carlos Pérez-Sánchez Miriam Ruiz-Ponce Julio Manuel Martínez-Moreno Eva Pérez-Pampin Antonio González Chamaida Plasencia-Rodriguez Ana Martínez-Feito Alejandro Balsa Clementina López-Medina Lourdes Ladehesa-Pineda Marta Rojas-Giménez Rafaela Ortega-Castro Jerusalem Calvo-Gutiérrez Chary López-Pedrera Eduardo Collantes-Estévez Iván Arias-de la Rosa Nuria Barbarroja Nuria Barbarroja Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling Frontiers in Immunology rheumatoid arthritis methotrexate tofacitinib biomarkers proximity extension assay (PEA) Olink |
| title | Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling |
| title_full | Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling |
| title_fullStr | Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling |
| title_full_unstemmed | Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling |
| title_short | Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling |
| title_sort | exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling |
| topic | rheumatoid arthritis methotrexate tofacitinib biomarkers proximity extension assay (PEA) Olink |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1333995/full |
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