dc.contributor.author | Ruiz Romero, Cristina | |
dc.contributor.author | Fernández Puente, Patricia | |
dc.contributor.author | González, L. | |
dc.contributor.author | Illiano, A. | |
dc.contributor.author | Lourido Salas, Lucía | |
dc.contributor.author | Paz, R. | |
dc.contributor.author | Quaranta Díaz, Patricia | |
dc.contributor.author | Pérez Pampín, Eva | |
dc.contributor.author | González Martínez-Pedrayo, Antonio | |
dc.contributor.author | Blanco García, Francisco | |
dc.contributor.author | Calamia ., Valentina | |
dc.date.accessioned | 2025-08-26T10:52:12Z | |
dc.date.available | 2025-08-26T10:52:12Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Ruiz-Romero C, Fernández-Puente P, González L, Illiano A, Lourido L, Paz R, et al. Association of the serological status of rheumatoid arthritis patients with two circulating protein biomarkers: A useful tool for precision medicine strategies. Frontiers in Medicine. 2022;9. | |
dc.identifier.issn | 2296-858X | |
dc.identifier.other | https://portalcientifico.sergas.gal/documentos/638be9d0840d3a6d9ac81a75 | * |
dc.identifier.uri | http://hdl.handle.net/20.500.11940/20714 | |
dc.description.abstract | Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and presence of systemic autoantibodies, with a great clinical and molecular heterogeneity. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are routinely used for the diagnosis of RA. However, additional serological markers are needed to improve the clinical management of this disease, allowing for better patient stratification and the desirable application of precision medicine strategies. In the present study, we investigated those systemic molecular changes that are associated with the RF and ACPA status of RA patients. To achieve this objective, we followed a proteomic biomarker pipeline from the discovery phase to validation. First, we performed an iTRAQ-based quantitative proteomic experiment on serum samples from the RA cohort of the Hospital of Santiago de Compostela (CHUS). In this discovery phase, serum samples from the CHUS cohort were pooled according to their RF/ACPA status. Shotgun analysis revealed that, in comparison with the double negative group (RF-/ACPA-), the abundance of 12 proteins was altered in the RF+/ACPA+ pool, 16 in the RF+/ACPA- pool and 10 in the RF-/ACPA+ pool. Vitamin D binding protein and haptoglobin were the unique proteins increased in all the comparisons. For the verification phase, 80 samples from the same cohort were analyzed individually. To this end, we developed a Multiple Reaction Monitoring (MRM) method that was employed in a comprehensive targeted analysis with the aim of verifying the results obtained in the discovery phase. Thirty-one peptides belonging to 12 proteins associated with RF and/or ACPA status were quantified by MRM. In a final validation phase, the serum levels of alpha-1-acid glycoprotein 1 (A1AG1), haptoglobin (HPT) and retinol-binding protein 4 (RET4) were measured by immunoassays in the RA cohort of the Hospital of A Coruña (HUAC). The increase of two of these putative biomarkers in the double seropositive group was validated in 260 patients from this cohort (p = 0.009 A1AG1; p = 0.003 HPT). The increased level of A1AG1 showed association with RF rather than ACPA (p = 0.023), whereas HPT showed association with ACPA rather than RF (p = 0.013). Altogether, this study has allowed a further classification of the RA seropositive patients into two novel clusters: RF+A1AG+ and ACPA+HPT+. The determination of A1AG1 and HPT in serum would provide novel information useful for RA patient stratification, which could facilitate the effective implementation of personalized medicine in routine clinical practice. | en |
dc.description.sponsorship | This study has been funded by Instituto de Salud Carlos III through the projects PI16/02124, PI17/00404, PI19/01206, PI20/00793, RETIC-RIER RD16/0012/0002, and RICORS-REI RD21/0002/0009 (co-funded by European Regional Development Fund/European Social Fund; A way to make Europe/Investing in your future). This study was also supported by AE CICA-INIBIC (ED431E 2018/03) and grants IN607A2021/07 and IN607D2020/10 from Xunta de Galicia. The Biomedical Research Networking Center (CIBER) is an initiative from Instituto de Salud Carlos III (ISCIII). PF-P was supported by Contrato PTA (PTA2017-14846-I), Ministerio de Ciencia, Innovacion y Universidades. LL was supported by Contrato Sara Borrell (CD19/00229), Fondo de Investigacion Sanitaria, ISCIII. VC is supported by RETIC-RIER RD16/0012/0002 and RICORS-REI RD21/0002/0009. Funding for open access charge: Universidade da Coruna/CISUG. | en |
dc.language.iso | eng | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Association of the serological status of rheumatoid arthritis patients with two circulating protein biomarkers: A useful tool for precision medicine strategies | * |
dc.type | Article | en |
dc.authorsophos | Ruiz-Romero, V. C. | |
dc.authorsophos | Fernández-Puente, P. | |
dc.authorsophos | González, L. | |
dc.authorsophos | Illiano, A. | |
dc.authorsophos | Lourido, L. | |
dc.authorsophos | Paz, R. | |
dc.authorsophos | Quaranta, P. | |
dc.authorsophos | Perez-Pampín, E. | |
dc.authorsophos | González, A. | |
dc.authorsophos | Blanco, F. J. | |
dc.authorsophos | Calamia | |
dc.identifier.doi | 10.3389/fmed.2022.963540 | |
dc.identifier.sophos | 638be9d0840d3a6d9ac81a75 | |
dc.journal.title | Frontiers in Medicine | * |
dc.relation.projectID | Instituto de Salud Carlos III; RETIC-RIER [PI16/02124, PI19/01206, PI20/00793]; RICORS-REI [RD16/0012/0002]; European Regional Development Fund/European Social Fund [RD21/0002/0009]; AE CICA-INIBIC; Xunta de Galicia [ED431E 2018/03]; Contrato PTA [IN607A2021/07, IN607D2020/10]; Ministerio de Ciencia, Innovacion y Universidades [PTA2017-14846-I]; Contrato Sara Borrell; Fondo de Investigacion Sanitaria [CD19/00229]; Universidade da Coruna/CISUG; ISCIII | |
dc.relation.publisherversion | https://www.frontiersin.org/articles/10.3389/fmed.2022.963540/pdf;https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.963540/pdf | es |
dc.rights.accessRights | openAccess | |
dc.subject.keyword | AS Coruña | es |
dc.subject.keyword | CHUAC | es |
dc.subject.keyword | INIBIC | es |
dc.subject.keyword | AS Santiago | es |
dc.subject.keyword | CHUS | es |
dc.subject.keyword | IDIS | es |
dc.typefides | Artículo Científico (incluye Original, Original breve, Revisión Sistemática y Meta-análisis) | es |
dc.typesophos | Artículo Original | es |
dc.volume.number | 9 | |