Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors
This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA pati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/3/382 |
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| author | Daniel Sobral Ana Filipa Fernandes Miguel Bernardes Patrícia Pinto Helena Santos João Lagoas-Gomes José Tavares-Costa José A. P. Silva João Madruga Dias Alexandra Bernardo Jean-Charles Gaillard Jean Armengaud Vladimir Benes Lúcia Domingues Sara Maia Jaime C. Branco Ana Varela Coelho Fernando M. Pimentel-Santos |
| author_facet | Daniel Sobral Ana Filipa Fernandes Miguel Bernardes Patrícia Pinto Helena Santos João Lagoas-Gomes José Tavares-Costa José A. P. Silva João Madruga Dias Alexandra Bernardo Jean-Charles Gaillard Jean Armengaud Vladimir Benes Lúcia Domingues Sara Maia Jaime C. Branco Ana Varela Coelho Fernando M. Pimentel-Santos |
| author_sort | Daniel Sobral |
| collection | DOAJ |
| description | This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (<i>n</i> = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and <i>AFF3</i>, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered. |
| first_indexed | 2024-04-24T18:29:47Z |
| format | Article |
| id | doaj.art-1ce5cc21929546879b104f7e022fd28b |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-24T18:29:47Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-1ce5cc21929546879b104f7e022fd28b2024-03-27T13:28:07ZengMDPI AGBiomolecules2218-273X2024-03-0114338210.3390/biom14030382Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor InhibitorsDaniel Sobral0Ana Filipa Fernandes1Miguel Bernardes2Patrícia Pinto3Helena Santos4João Lagoas-Gomes5José Tavares-Costa6José A. P. Silva7João Madruga Dias8Alexandra Bernardo9Jean-Charles Gaillard10Jean Armengaud11Vladimir Benes12Lúcia Domingues13Sara Maia14Jaime C. Branco15Ana Varela Coelho16Fernando M. Pimentel-Santos17Applied Molecular Biosciences Unit, Life Sciences Department, Sciences and Technology School, NOVA University of Lisbon, 2829-516 Caparica, PortugalInstituto de Tecnologia Química e Biológica António Xavier, Nova University of Lisbon, Av. Da República, 2780-157 Oeiras, PortugalDepartment of Medicine, Faculty of Medicine, University of Porto, 4099-002 Porto, PortugalRheumatology Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, 4434-502 Vila Nova de Gaia, PortugalNOVA Medical Research, NOVA Medical School, NOVA University of Lisbon, 1169-056 Lisbon, PortugalRheumatology Department, Centro Hospitalar do Tâmega e Sousa, Hospital Padre Américo, 4560-136 Penafiel, PortugalRheumatology Department, Unidade Local de Saúde do Alto Minho, 4990-078 Ponte de Lima, PortugalI.CBR—Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalNOVA Medical Research, NOVA Medical School, NOVA University of Lisbon, 1169-056 Lisbon, PortugalRheumatology Department, Centro Hospitalar e Universitário de São João, 4200–319 Porto, PortugalDépartement Médicaments et Technologies pour la Santé (DMTS), Université Paris-Saclay, CEA, INRAE, SPI, F-30200 Bagnols-sur-Cèze, FranceDépartement Médicaments et Technologies pour la Santé (DMTS), Université Paris-Saclay, CEA, INRAE, SPI, F-30200 Bagnols-sur-Cèze, FranceEMBL Genomics Core Facility, Meyerhofstr. 1, D-69117 Heidelberg, GermanyNOVA Medical Research, NOVA Medical School, NOVA University of Lisbon, 1169-056 Lisbon, PortugalNOVA Medical Research, NOVA Medical School, NOVA University of Lisbon, 1169-056 Lisbon, PortugalNOVA Medical Research, NOVA Medical School, NOVA University of Lisbon, 1169-056 Lisbon, PortugalInstituto de Tecnologia Química e Biológica António Xavier, Nova University of Lisbon, Av. Da República, 2780-157 Oeiras, PortugalNOVA Medical Research, NOVA Medical School, NOVA University of Lisbon, 1169-056 Lisbon, PortugalThis study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (<i>n</i> = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and <i>AFF3</i>, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.https://www.mdpi.com/2218-273X/14/3/382axial spondyloarthritisTNF inhibitor (adalimumab)treatment responsedisease activityinnate immune systemadaptive immune system |
| spellingShingle | Daniel Sobral Ana Filipa Fernandes Miguel Bernardes Patrícia Pinto Helena Santos João Lagoas-Gomes José Tavares-Costa José A. P. Silva João Madruga Dias Alexandra Bernardo Jean-Charles Gaillard Jean Armengaud Vladimir Benes Lúcia Domingues Sara Maia Jaime C. Branco Ana Varela Coelho Fernando M. Pimentel-Santos Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors Biomolecules axial spondyloarthritis TNF inhibitor (adalimumab) treatment response disease activity innate immune system adaptive immune system |
| title | Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors |
| title_full | Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors |
| title_fullStr | Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors |
| title_full_unstemmed | Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors |
| title_short | Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors |
| title_sort | molecular profiling of axial spondyloarthritis patients reveals an association between innate and adaptive cell populations and therapeutic response to tumor necrosis factor inhibitors |
| topic | axial spondyloarthritis TNF inhibitor (adalimumab) treatment response disease activity innate immune system adaptive immune system |
| url | https://www.mdpi.com/2218-273X/14/3/382 |
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